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BIOMARKER:

CHEK1 mutation

i
Other names: CHEK1, CHK1, Checkpoint kinase 1
Entrez ID:
Related biomarkers:
Related tests:
2ms
Trial completion • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
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HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • PTEN mutation + HR positive • CHEK1 expression • HER-2 negative + HR positive + BRCA mutation
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Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)
2ms
Circulating Tumor DNA (ctDNA) Monitoring in the Assessment and Prediction of the Efficacy of PARP Inhibitors (PARPi) (clinicaltrials.gov)
P=N/A, N=30, Recruiting, Sun Yat-sen University | Trial completion date: Aug 2023 --> Aug 2025
Trial completion date • Circulating tumor DNA
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • BRCA1 mutation + ATM mutation • CHEK1 expression
7ms
Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)
P1, N=44, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting
Enrollment open • Metastases
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
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Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)
9ms
ORCHID: Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (clinicaltrials.gov)
P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2025
Trial completion date • Trial primary completion date • Metastases
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
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Lynparza (olaparib)
9ms
Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)
P1, N=44, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
Enrollment closed
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
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Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)
11ms
Efficacy of olaparib (O) plus abiraterone (A) versus placebo (P) plus A in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with single homologous recombination repair gene mutations (HRRm) in the PROpel trial. (ASCO-GU 2024)
BRCA2, ATM and CDK12 were the most prevalent single gene mutations and clinical benefit was observed with O + A. Other single gene mutations were rare, limiting interpretation. The greatest treatment benefit was observed in pts with BRCA mutations. Clinical trial information: NCT03732820.NR, not reached; BRIP1, RAD51B, RAD51D n=1; CHEK1, RAD51C n=0.
Clinical • PARP Biomarker • BRCA Biomarker • Metastases
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
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ATM mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BRCA mutation • CHEK1 mutation • BRCA2 mutation + ATM mutation • CHEK1 expression
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FoundationOne® CDx • FoundationOne® Liquid CDx
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Lynparza (olaparib) • abiraterone acetate
11ms
Real-world homologous recombination repair mutation (HRRm) testing patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in the United States. (ASCO-GU 2024)
Pts with confirmed mCRPC diagnosis, age ≥21 years, treated with olaparib monotherapy after exposure to abiraterone or enzalutamide, and with positive HRRm status were included. This real-world analysis highlights the need for earlier HRRm testing in pts with mCRPC to allow for optimal timing of novel treatment options that have shown efficacy in a biomarker-selected population. Most pts in this study were tested and diagnosed with HRRm many months after mCRPC diagnosis, at which point they had high levels of bone metastasis, multiple sites of distant metastases, and opioid use at the initiation of olaparib treatment. HRR testing in pts before or at the time of mCRPC would allow for olaparib therapy earlier in the disease course.
Real-world evidence • Clinical • PARP Biomarker • BRCA Biomarker • Real-world • Metastases
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
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BRCA1 mutation • ATM mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
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Lynparza (olaparib) • Xtandi (enzalutamide capsule) • abiraterone acetate
1year
Whole Exome Sequencing reveals clinically important pathogenic mutations in DNA repair genes across lung cancer patients. (PubMed, Am J Cancer Res)
The observed pathogenic mutations in BRCA1, BRCA2, ERCC6, CHEK1, MUTYH, and RAD51D, coupled with their down-regulation and hypermethylation, suggest a potential convergence of genetic and epigenetic factors driving genomic instability in lung cancer cells. These findings contribute to our understanding of lung cancer susceptibility and highlight potential avenues for targeted therapeutic interventions in Pakistani lung cancer patients.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • MUTYH (MutY homolog) • ERCC6 (Excision repair cross-complementation group 6)
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BRCA2 mutation • BRCA1 mutation • RAD51D mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
1year
The role of DNA repair genes mutational status in prostate cancer treatment with androgen signaling blockade (EMUC 2023)
Probably, the data obtained on the worst efficacy of enzalutamide after docetaxel in patients with mutations in  HRR genes can be attributed to the biological features of the influence of therapy methods on the course of the disease. In clinical practice, it is advisable to take into account the fact of the influence of previous treatment on the effectiveness of antiandrogenic therapy in choosing the sequence of treatment methods.
BRCA Biomarker
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KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51B mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression
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docetaxel • Xtandi (enzalutamide capsule)
1year
Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
P2, N=50, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2023 --> May 2023
Enrollment closed • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
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Lynparza (olaparib)
1year
The Genomic Landscape of Colorectal Cancer in the Saudi Arabian Population Using a Comprehensive Genomic Panel. (PubMed, Diagnostics (Basel))
These results may help optimize personalized therapy when drugs specific to a patient's mutation profile have already been developed.
Journal • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • PMS2 (PMS1 protein homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • CHEK1 (Checkpoint kinase 1) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
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ATM mutation • PMS2 mutation • CHEK1 mutation • CHEK1 expression
1year
Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2024 --> Feb 2025
Trial completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
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Lynparza (olaparib)
1year
Ovarian High-grade Serous Carcinoma with Transitional-like (SET) Morphology: A Homologous Recombination-deficient Tumor. (PubMed, Hum Pathol)
"Our results show that the majority of HGSCs with SET features are homologous recombination deficient tumors independently of the BRCA status and highlight the importance of the homologous recombination repair tumor testing especially in BRCA wild-type tumors. Recognition of transitional cell variant of HGSCs may help to identify patients most likely to benefit from PARP inhibitors."
Journal
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • BRCA wild-type • CDK12 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression
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Myriad myChoice® CDx Plus • SOPHiA DDM HRD Solution
over1year
Application value of whole exon sequencing and immune related indicators in the precision treatment of oral squamous cell carcinoma (PubMed, Beijing Da Xue Xue Bao Yi Xue Ban)
The present results do not support the wide application and promotion of genetic testing and immune related indexes in OSCC.
Journal • Tumor mutational burden • IO biomarker
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CHEK1 (Checkpoint kinase 1) • HLA-B (Major Histocompatibility Complex, Class I, B)
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TP53 mutation • CHEK1 mutation • CHEK1 expression
over1year
Homologous recombination repair (HRR) gene mutation: A novel biomarker for precision genomics testing in advanced lung cancer (ESMO 2023)
Table: 1429P Conclusions The HRR gene mutation in advanced lung cancer was independent of the predictors for immunotherapy response (TMB, MSI and PD-L1 biomarkers). Further clinical trials are needed to assess the efficacy of combining poly ADP ribose polymerase (PARP) inhibitors with immunotherapy in the future.
Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker • Metastases
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TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA2 mutation • ATM mutation • ARID1A mutation • CDK12 mutation • BRIP1 mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • BRCA mutation • CHEK1 mutation • CHEK1 expression
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FoundationOne® CDx
over1year
HRD status of patients with early stage non-small cell lung cancer (ESMO 2023)
Preliminary functional experiments in HRP (HR proficient, n=5) and HRD (n=4) PDX and organoids (n=3 and n=3 for HRD and HRP respectively) indicate that HRD tumors present low RAD51 foci count (p=0.03 after damage induction) and favorable response to Olaparib and CDDP. Conclusions These data suggest that homologous recombination may be deficient in a substantial proportion of early-stage NSCLC patients, supporting the potential use of PARPi in HRD patients in the adjuvant or maintenance setting.
Clinical • PARP Biomarker • BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1)
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BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • CHEK2 mutation • HRD + BRCA1 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
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AmoyDx® HRD Focus Panel
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Lynparza (olaparib)
over1year
Clinical significance of DNA damage response mutations in early stage NSCLC (ESMO 2023)
Deleterious mutations in ATM, BRCA1/2, CHEK1, BARD1 and BRIP1 were independent prognostic indicators of significantly longer disease-free survival. Conclusions Deleterious mutations of these six genes were common in early-stage NSCLC and may serve as prognostic biomarkers.
Clinical • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CD8 (cluster of differentiation 8) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1)
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PD-L1 expression • BRCA2 mutation • BRCA1 mutation • ATM mutation • BRIP1 mutation • CD8 positive • BARD1 mutation • CHEK1 mutation • CHEK1 expression
over1year
LP-184, a Tumor Site Activated Small Molecule Acylfulvene, Is Effective Preclinically in Subsets of Lung Cancer (IASLC-WCLC 2023)
H460 KEAP1/STK11 mutant cell line derived xenograft model was used to demonstrate the anti-tumor activity of LP-184. LP-184 displayed strong nanomolar potency in 7 day ex vivo treatment in a panel of patient derived lung cancer models carrying ATM, BRCA1 or CHEK1 mutations with IC50s in the range of 30 - 200 nM, which turned out to be 12-350 times superior to that of Olaparib across the same models. LP-184 is highly effective in selected molecular subsets of lung cancer in proof-of-concept ex vivo and in vivo studies, supporting its clinical development in small cell and non-small cell lung cancers. IND-enabling repeat dose GLP toxicology studies of LP-184 show it to be well tolerated in rats and dogs. A first-in-human dose escalation Phase 1A trial with LP-184 is expected to enroll all advanced solid tumors including lung cancers.
Preclinical • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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BRCA1 (Breast cancer 1, early onset) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • KEAP1 (Kelch Like ECH Associated Protein 1) • CHEK1 (Checkpoint kinase 1) • PTGR1 (Prostaglandin Reductase 1) • RNF168 (Ring Finger Protein 168)
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HRD • STK11 mutation • KEAP1 mutation • CHEK1 mutation • KEAP1 expression • PTGR1 expression • CHEK1 expression
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Lynparza (olaparib) • hydroxyureamethylacylfulvene (STAR-001)
over1year
HRR Gene Mutations- A New Biomarker for Precision Genomics Based Testing in Metastatic Lung Cancer (IASLC-WCLC 2023)
The emphasis on precision genomics-based targeted therapy in metastatic lung cancer is evolving rapidly and the addition of new HRR genes-based biomarker testing in lung cancer promotes opportunity for further clinical trials to assess the efficacy of combining PARP inhibitors with Immunotherapy in the future.
Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IL1R1 (Interleukin 1 receptor, type I) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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PD-L1 expression • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • ATM mutation • ARID1A mutation • PD-L1 negative • PALB2 mutation • CDK12 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • BRCA mutation • CHEK1 mutation • FANCG mutation • RAD51 mutation • CHEK1 expression
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FoundationOne® CDx
over1year
The Genomic Landscape of Colorectal Cancer in the Saudi Arabian Population (AMP Europe 2023)
In conclusion, we present a mutational landscape of actionable genes in CRC for the SA population in patients without a familial history of CRC. Additionally, we address the clinical relevance of low variant allele frequency variants. A comprehensive analysis of population-specific molecular markers for CRC can provide insights into the disease progression, with an aim of optimizing individualized therapeutic options and treatment regimens in the management of CRC in the SA population.
Clinical • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • PMS2 (PMS1 protein homolog 2) • CHEK1 (Checkpoint kinase 1) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
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ATM mutation • PMS2 mutation • CHEK1 mutation • CHEK1 expression
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Oncomine™ Comprehensive Assay v3M
over1year
P2 data • Clinical • Tumor mutational burden • PARP Biomarker • BRCA Biomarker • Metastases
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • NPM1 (Nucleophosmin 1) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • MUTYH (MutY homolog) • BRD4 (Bromodomain Containing 4) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • FANCC (FA Complementation Group C)
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TMB-H • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • BARD1 mutation • CHEK1 mutation • FANCG mutation • CHEK1 expression
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FoundationOne® CDx
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Lynparza (olaparib)
over1year
The Prevalence of CHEK1 and CHEK2 Mutations in Prostate Cancer: a Retrospective Cohort Study. (PubMed, Med Arch)
No association was found in this study between CHEK1 mutations and the development of PCa. Further studies are needed with larger cohorts along with a screening of more exons in order to shed more light on the frequency of CHEK2 gene mutations and their role in the development of PCa in Jordan.
Retrospective data • Journal
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CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
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CHEK2 mutation • CHEK1 mutation • CHEK1 expression
over1year
LP-184, an acylfulvene class small molecule therapeutic, is synthetically lethal in DNA damage repair deficient cancers (AACR 2023)
LP-184 treatment resulted in complete tumor regression (107-141% TGI) in 10/10 HR deficient triple negative breast cancer PDX models of which 7/10 were resistant Olaparib/ Niraparib and to Doxorubicin/ Cyclophosphamide. Unlike PARPi, LP-184 has striking activity in both NERD as well as HRD cancers. These strong data have prompted the development of a soon to be launched clinical trial to translate the broad preclinical anticancer activity of LP-184 in solid tumors with HR/NER pathway defects, such as pancreatic, prostate, ovarian and breast cancers.
BRCA Biomarker • PARP Biomarker • Synthetic lethality
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • ERCC1 (Excision repair cross-complementation group 1) • ERCC2 (Excision repair cross-complementation group 2) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • ATR (Ataxia telangiectasia and Rad3-related protein) • CHEK1 (Checkpoint kinase 1) • PTGR1 (Prostaglandin Reductase 1)
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BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • HRD + BRCA1 mutation • FANCA mutation • CHEK1 mutation • PTGR1 expression • RAD51 mutation • CHEK1 expression
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Lynparza (olaparib) • doxorubicin hydrochloride • Zejula (niraparib) • cyclophosphamide • hydroxyureamethylacylfulvene (STAR-001)
over1year
Pan-cancer proteogenomics expands the landscape of therapeutic targets (AACR 2023)
Based on tumor proteogenomic data and cell line CRISPR-Cas9 screen data, we identified synthetic lethality for difficult to target tumor suppressor losses, revealing TP53 mutations as a candidate biomarker to select breast cancer patients for CHEK1 inhibition, and endometrial cancer patients for treatment with doxorubicin... We generate a comprehensive resource of protein and peptide targets that covers multiple therapeutic modalities. This unique resource will pave the way for repurposing of currently available drugs and developing new drugs for cancer treatment.
IO Companion diagnostic • IO biomarker • Pan tumor
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TP53 (Tumor protein P53) • HLA-A (Major Histocompatibility Complex, Class I, A) • CHEK1 (Checkpoint kinase 1) • PTPN1 (Protein Tyrosine Phosphatase Non-Receptor Type 1)
|
TP53 mutation • HLA-A*02 • CHEK1 mutation • CHEK1 expression
|
doxorubicin hydrochloride
over1year
ORCHID: Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (clinicaltrials.gov)
P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2023 --> Mar 2024
Trial completion date • Trial primary completion date • Metastases
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
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Lynparza (olaparib)
almost2years
Profiling of the genetic features of Chinese patients with gastric cancer with HRD germline mutations in a large-scale retrospective study. (PubMed, J Med Genet)
Our data suggest that carrying both HRD and MMR gene LoF germline mutations may cause early-onset GC. Germline mutations in the HRD gene should be of concern in the study of hereditary GC.
Retrospective data • Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • FANCL (FA Complementation Group L)
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BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • HRD + BRCA1 mutation • FANCA mutation • CHEK1 mutation • CHEK1 expression
2years
Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2023 --> Feb 2024 | Trial primary completion date: Sep 2022 --> Sep 2023
Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
|
Lynparza (olaparib)
2years
Clinical • P2 data • Combination therapy • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • ATRX mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
|
Lynparza (olaparib) • abiraterone acetate • prednisone
over2years
The Prevalence of CHEK 1 and CHEK 2 mutations in prostate cancer in Jordan population: a retrospective cohort study (ECP 2022)
We found, and in line with previous studies, lack of association between CHEK1 mutations and PCa development. The presence of 1.4% of mutation in CHEK2 in our results supported the possible role of genetic variants in this gene and the develop-ment of PCa. Further studies are needed with larger cohorts to shed more light on these findings and to reveal the genetic predisposi-tion of the CHEK2 gene in the development of PCa in Jordan and perform screening of more exons.
Retrospective data
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CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)
|
CHEK2 mutation • CHEK1 mutation • CHEK1 expression
over2years
Concurrent loss of MLH1, PMS2 and MSH6 immunoexpression in gastrointestinal cancer indicating a widespread dysregulation in DNA reparation processes (ECP 2022)
Our study suggests that the simultaneous loss of MLH1, PMS2 and MSH6 immunoexpression among diferent gastrointesti-nal cancers is associated with and potentially even based on more widespread alterations in DNA repair processes. Next-generation sequencing could reveal further mutations in additional DNA repair-related genes in the present cases. With the advent of drugs targeting DNA repair in clinical practice, especially PARP-inhibitors, and their potential indication extension for mutations other than BRCA1/2 such as PALB2 our results are of immediate clinical signifcance.
BRCA Biomarker • PARP Biomarker
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BRAF (B-raf proto-oncogene) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • FANCA (FA Complementation Group A) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54)
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BRAF V600E • BRCA2 mutation • BRCA1 mutation • BRAF V600 • ATM mutation • PALB2 mutation • FANCA mutation • RAD51D mutation • PMS2 mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression • MSH6 expression
over2years
CHANGEABLE: Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=37, Recruiting, Fudan University | Not yet recruiting --> Recruiting | Trial completion date: Apr 2022 --> Dec 2022 | Trial primary completion date: Feb 2022 --> Nov 2022
Enrollment open • Trial completion date • Trial primary completion date
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HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCC (FA Complementation Group C)
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HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • CHEK1 expression
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Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)
over2years
Genomic and immunologic profiles of concurrent RB1 and CDKN1A/p21(WAF1) truncating mutations (RW+) in bladder cancer. (ASCO 2022)
Truncating WAF1 mutations are associated with sensitivity to cisplatin and are associated with truncating Rb mutations in bladder cancer (RW+)... Concurrent truncating mutation in RB1 and WAF1 (RW+) bladder carcinomas have fewer p53, ARID1A, and PIK3CA mutations but are enriched for E2F targets, G2/M checkpoint genes, FANCC/A, CHEK1, WEE1, CDC25A/C, PALB2 and BRCA1/2 and have a distinct immunological profile. The findings suggest therapeutic strategies for RW+ bladder cancers including Chk1/Wee1, PARP inhibitors, -/+ immunotherapy that may impact on clinical outcomes.
PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR3 (Fibroblast growth factor receptor 3) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CDC25A (Cell Division Cycle 25A) • FANCC (FA Complementation Group C) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)
|
TP53 mutation • PIK3CA mutation • ARID1A mutation • PALB2 mutation • FGFR3 mutation • RB1 mutation • CHEK1 mutation • CHEK1 expression
|
MI Tumor Seek™
|
cisplatin
over2years
ORCHID: Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (clinicaltrials.gov)
P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Mar 2022 --> Mar 2023
Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
|
Lynparza (olaparib)
over2years
Pan-cancer analysis revealed characteristics of reversion mutations in homologous recombination repair genes (AACR 2022)
This study analyzed clinical and mutational characteristics of reversion mutations in HRR genes, which could occur as single or multiple variants to restore the function of predisposed pathogenic HRR mutations, resulting in resistance to platinum-based chemotherapies or PARP inhibitors. Monitoring these mutations with tissue or liquid biopsy samples are crucial for treatment guidance.
BRCA Biomarker • PARP Biomarker • Pan tumor
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • WRN (WRN RecQ Like Helicase) • FANCI (FA Complementation Group I) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • FANCD2 (FA Complementation Group D2) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • MRE11A mutation • RAD54L mutation • NBN mutation • WRN mutation • FANCI mutation • CHEK1 expression
over2years
Effects of homologous recombination-related gene mutation subtypes on gene instability and the efficacy of platinum-containing regiments in triple-negative breast cancer (AACR 2022)
In this study, we found that different HR-related genes mutation subtypes may exert distinct effects on genomic instability, and mutations in HR-related genes beyond the context of BRCA1/2 may serve as a biomarker for platinum-based adjuvant therapy for TNBC patients, which warrants further studies.
Clinical • BRCA Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
|
BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression • High HRD score
over2years
Trial completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression
|
FoundationOne® CDx
|
berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
almost3years
Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2022 --> Feb 2023 | Trial primary completion date: Jan 2022 --> Sep 2022
Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
|
Lynparza (olaparib)
almost3years
Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)
P1, N=44, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting
Enrollment open
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
|
Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)
almost3years
Analysis of the role of PI3K-AKT and DNA damage repair (DDR) genomic biomarkers as predictors of clinical outcomes in non-metastatic castration-resistant prostate cancer (nmCRPC). (ASCO-GU 2022)
Of the 37 patients included, 30 (82%) received apalutamide, 5 (13%) received darolutamide, and 2 (6%) received enzalutamide...Of those who had subsequent treatment, 1 received enzalutamide and 5 received abiraterone... This final analysis demonstrates that nmCRPC with PI3K and DDR signalling pathway mutations have poor clinical outcomes when treated with ARAT, likely secondary to decreased reliance on the androgen receptor signalling pathway. These results highlight the potential value of exploring targeted therapies, such as PARP or AKT inhibitors in patients with these mutations.
Clinical • Clinical data • BRCA Biomarker • PARP Biomarker
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • MLH1 (MutL homolog 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) • CHEK1 (Checkpoint kinase 1) • FANCL (FA Complementation Group L) • PIK3C2B (Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta) • FANCD2 (FA Complementation Group D2) • PI3K (Phosphoinositide 3-kinases)
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PIK3CA mutation • ATM mutation • PTEN mutation • CDK12 mutation • CHEK2 mutation • MLH1 mutation • CHEK1 mutation • CHEK1 expression
|
Xtandi (enzalutamide capsule) • abiraterone acetate • Nubeqa (darolutamide) • Erleada (apalutamide)
almost3years
DNA damaging therapies in patients (pts) with prostate cancer (PC) and pathogenic alterations in homologous recombination repair (HRR) genes. (ASCO-GU 2022)
PC pts with BRCA1/2 mutations had improved outcomes to PARPi compared to those with mutations in HRR genes not directly interacting with the BRCA complex. Platinum-based chemo appeared effective regardless of which HRR gene was affected. Outcomes to DNA damaging therapies.
Clinical • BRCA Biomarker • PARP Biomarker
|
HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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BRCA2 mutation • BRCA1 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression
almost3years
Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)
P1, N=44, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Oct 2021 --> Dec 2021
Trial initiation date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
|
Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)
3years
New trial • Circulating tumor DNA
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression