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GENE:

CHEK2 (Checkpoint kinase 2)

News alerts, weekly reports and conference planners

p53 pathway genes’ mutations (muts) as prognostic factors in patients (pts) with metastatic Pancreatic Ductal Adenocarcinoma (mPDAC): a single center study (AIOM 2024)

Our study suggests an important prognostic role of p53 signaling muts in mPDAC pts; wt pts resulted in a longer OS than mutated pts, although some muts, in particular tp53 exon4 mut, seem to be associated with longer survival. Further studies are needed to investigate these findings, including an in-depth analysis of structural proteomics.

1 day ago

Clinical • Metastases

KRAS (KRAS proto-oncogene GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CHEK2 (Checkpoint kinase 2) • MDM4 (The mouse double minute 4) • CHEK1 (Checkpoint kinase 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)

TP53 mutation • KRAS mutation • TP53 wild-type • TP53 exon 4 mutation

TruSight Oncology 500 Assay

Mismatch Repair (MMR) and Homologous Recombination (HR) Deficiency: Real-Life Applications of biomarkers for complementary approaches in Epithelial Ovarian Cancer (AIOM 2024)

HRD genomic instability tests and multigene panel assessments serve as synergistic tools in EOC clinical settings, proving essential for identifying patients likely to benefit from PARPi therapy. These tools also enhance the detection of HRR and MMR gene variants, aiding in preventive care. Further investigations into the genetic profiles of HRD-negative tumors are crucial for advancing cancer risk management and developing novel therapeutic avenues.

1 day ago

Clinical • Mismatch repair • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MUTYH (MutY homolog)

BRCA2 mutation • BRCA1 mutation • HRD • BRCA wild-type

Myriad myChoice® CDx

Homologous recombination (HR) and DNA damage repair (DDR) somatic alterations in metastatic colorectal cancer (mCRC): results from the comprehensive genomic profiling (CGP) trial FPG500 (AIOM 2024)

Background : Treatment (tx) of MSS/MMRp mCRC relies mainly on oxaliplatin (oxa)- or irinotecan-based doublet chemotherapy regimens, with no biomarker reported so far, allowing the selection of one tx over the other. HR-DDRa is associated with MSI-H or TMB-H. Pts with MSS HR-DDRa tumors benefit from oxa-based first line treatment. Longer FU, allowing mature OS data, and wider cohorts are warranted.

1 day ago

Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Metastases

TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • 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)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

TMB-H • MSI-H/dMMR

TruSight Oncology 500 Assay

oxaliplatin • irinotecan

Germline pathogenic variants in prostate cancer. (PubMed, Pathol Res Pract)

Individuals with a family history of cancer were significantly more likely to have a pathogenic or likely pathogenic variant than those without one (p = 0.002). Overall, our results show the necessity for future research with a larger sample size to better explain the relationship between clinicopathologic data and genetic variants.

1 day ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • HOXB13 (Homeobox B13) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)

Guarding against digestive-system cancers: Unveiling the role of Chk2 as a potential therapeutic target. (PubMed, Genes Dis)

In addition, we summarize evidence indicating that Chk2 can serve as a novel therapeutic target, based on its contributions to radiochemotherapy-resistance reversion and progress made in developing antitumor agents against Chk2. The prevailing evidence supports the conclusion that further research on Chk2 will provide a deeper understanding of digestive-system tumorigenesis and should suggest novel therapeutic targets.

2 days ago

Review • Journal

CHEK2 (Checkpoint kinase 2)

A case of a patient at reproductive age with BRCA2 and CHEK2 mutations and multiple uterine fibroids. (PubMed, Ginekol Pol)

No abstract available

3 days ago

Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2)

CHEK2 mutation • BRCA2 mutation + CHEK2 mutation

Pathogenic variants in cancer susceptibility genes predispose to Ductal Carcinoma In situ of the breast. (PubMed, Clin Cancer Res)

The enrichment of PVs in ATM, BRCA1, BRCA2, CHEK2 and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of contralateral breast cancer in carriers of PVs in high penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.

3 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

Panobinostat Synergizes with Chemotherapeutic Agents and Improves Efficacy of Standard-of-Care Chemotherapy Combinations in Ewing Sarcoma Cells. (PubMed, Cancers (Basel))

The combination of Panobinostat with Doxorubicin or Etoposide, both of which are used as standard of care in upfront treatment, leads to a synergistic effect in EWS cells. Overall, our data indicate that HDAC2 is overexpressed in many EWS tumor samples and HDAC inhibition is effective in targeting EWS cells, alone and in combination with standard-of-care chemotherapy agents. This work suggests that the addition of an HDAC inhibitor to upfront treatment may improve response.

3 days ago

Journal

ALK (Anaplastic lymphoma kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CHEK2 (Checkpoint kinase 2) • JAK1 (Janus Kinase 1) • CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • HDAC2 (Histone deacetylase 2)

CCND1 expression • HDAC2 expression

doxorubicin hydrochloride • etoposide IV • Farydak (panobinostat)

BRCA2 and TP53 Mutations in a Breast Cancer Patient: A Case Report and Review of the Literature. (PubMed, Cureus)

Multigene tests are essential in the treatment approach to young BC patients, since the detection of specific mutations may help guide changes in preventive measures and treatment plans. This report describes a rare case of BC in a young patient with pathogenic germline variants in BRCA2 and TP53 genes and also presents a literature review of the topic.

3 days ago

Review • Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)

TP53 mutation • BRCA2 mutation + TP53 mutation

PLATPARP: A Trial of Niraparib in Platinum-Sensitive Castration-Resistant Prostate Cancer with DNA Repair Defects (clinicaltrials.gov)

P2, N=12, Completed, Abramson Cancer Center at Penn Medicine | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Feb 2024 | Trial primary completion date: Jun 2024 --> Feb 2024

6 days ago

Trial completion • Trial completion date • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • HDAC2 (Histone deacetylase 2)

Zejula (niraparib)

Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer with Homologous Recombination Deficiency That Has Spread to the Liver (clinicaltrials.gov)

P1, N=1, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2024

6 days ago

Trial completion • Trial completion date • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BAP1 (BRCA1 Associated Protein 1) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C)

BRCA1 mutation • PALB2 mutation

MSK-IMPACT

cisplatin • gemcitabine

11d

Prospective germline sequencing of patients with gliomas, glioneuronal or neuronal tumors (SNO 2024)

Clinical germline sequencing identifies a germline mutation in a high proportion of patients with CNS tumors. Biallelic inactivation was most commonly identified in tumors from patients with germline TP53 or NF1 mutations and were less common in patients with a germline MMR alteration.

11 days ago

Clinical • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

TP53 mutation • NF1 mutation • CHEK2 mutation • IDH wild-type

MSK-IMPACT

13d

Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer With Homologous Recombination Deficiency That Has Spread to the Liver (clinicaltrials.gov)

P1, N=1, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

13 days ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 mutation • PALB2 mutation

MSK-IMPACT

cisplatin • gemcitabine

16d

Clinical Outcomes and the 21-Gene Recurrence Score Assay in Early-Stage Breast Cancer Associated with CHEK2, ATM and PALB2 Germline Pathogenic Variants (SABCS 2024)

No abstract available

16 days ago

Clinical • Clinical data

PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)

Oncotype DX Breast Recurrence Score®Test

18d

Chidamide Combined with (+) -JQ-1 to Kill MLL-Rearrangement Acute Myeloid Leukemia Cells by Disrupting the DNA Damage Response Pathway (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)

Chidamide combined with (+)-JQ-1 can inhibit the proliferation of MLL-r AML cells, inhibit the initiation of protective self-repair of these leukemia cells by inhibiting the DNA damage response pathway, and ultimately increase the apoptosis of these cells, but non- MLL-r AML cells have no similar results.

18 days ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • KMT2A (Lysine Methyltransferase 2A) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • CHEK1 (Checkpoint kinase 1) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • BRD4 (Bromodomain Containing 4) • TP53BP1 (Tumor Protein P53 Binding Protein 1)

MLL rearrangement • MLL rearrangement • BCL2 expression • BAX expression

JQ-1 • Epidaza (chidamide)

18d

Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors. (PubMed, Mol Cancer)

Our data challenge the prevailing surface PDL1 paradigm, elucidate important and previously unappreciated roles for tumour-intrinsic PDL1 in regulating the ATM/Chk2 DNA damage response axis and E3 ligase-mediated protein degradation, suggest tumour PDL1 as a biomarker for Chk1i efficacy, and support the rapid clinical potential of pharmacologic tumour PDL1 depletion to treat selected cancers.

18 days ago

Journal • PD(L)-1 Biomarker • IO biomarker

CHEK2 (Checkpoint kinase 2)

PD-L1 expression

22d

Two Decades of Progress in Personalized Medicine of Colorectal Cancer in Serbia-Insights from the Institute for Oncology and Radiology of Serbia. (PubMed, Biomedicines)

Although significant improvements in CRC management have occurred globally in recent years, a strategic approach leading to population-based systemic solutions is required. The high incidence of young-onset CRC and the growing elderly population due to a rise in life expectancy will be especially important factors for countries with limited healthcare resources like Serbia.

22 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • APC (APC Regulator Of WNT Signaling Pathway) • RAS (Rat Sarcoma Virus) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

KRAS mutation • BRAF mutation • NRAS mutation • BRAF V600 • RAS mutation • CHEK2 mutation

27d

Strong association of single nucleotide polymorphisms in BRCA1, ATM, and CHEK2 with breast cancer susceptibility in a sub-population of Iranian women. (PubMed, Breast Cancer Res Treat)

Our results indicated that BRCA1, ATM, and CHEK2 polymorphisms have a high frequency in the Iranian breast cancer population, with some mutant allele frequencies being much higher than those reported in other populations. We have also provided a simple, multiplex, rapid, and accurate genotyping assay that is useful in clinical settings.

27 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2)

27d

Niraparib in Patients With Pancreatic Cancer (clinicaltrials.gov)

P2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

27 days ago

Trial completion date • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation

Zejula (niraparib)

29d

Phenotypic evaluation of deep learning models for classifying germline variant pathogenicity. (PubMed, NPJ Precis Oncol)

Model predictions for missense variants in BRCA1, BRCA2 and PALB2, but not ATM and CHEK2, were associated with breast cancer risk. However, deep learning models had limited clinical utility when specifically applied to variants of uncertain significance.

29 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)

ARID1A loss sensitizes colorectal cancer cells to floxuridine. (PubMed, Neoplasia)

Notably, we found that FUDR exhibited increased sensitivity in ARID1A-deficient cells compared to 5-fluorouracil (5-FU), a commonly used anticancer drug for CRC. In conclusion, ARID1A loss significantly heightens sensitivity to FUDR by promoting FUDR-induced DNA damage in CRC. These findings offer a novel therapeutic approach for the treatment of CRC characterized by ARID1A loss-of-function mutations.

1 month ago

Journal

ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • TYMS (Thymidylate Synthetase)

ARID1A mutation

5-fluorouracil

Association of Gene Variant Type and Location with Breast Cancer Risk in the General Population. (PubMed, medRxiv)

Women carrying protein truncating variants in exon 11 have a lower breast cancer risk in the population-based cohorts, older age at diagnosis and higher rates of estrogen receptor negative breast cancer than women with exon 1-10 or exon 13-27 truncation variants in population-based and clinical testing cohorts. Meaning: Incorporating pathogenic variant type and location in cancer risk models may improve individualized risk prediction.

1 month ago

Journal

ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)

ER negative

Case report: Germline CHEK2 mutation is associated with a giant cell glioblastoma. (PubMed, Front Oncol)

Additional mutations detected in the tumor included TP53, PTEN, and a PTPRZ1-MET fusion. This represents the first reported case of a CHEK2 germline mutation in giant cell glioblastoma, further supporting the significance of impaired DNA repair mechanisms in the development of this disease.

1 month ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)

TP53 mutation • PTEN mutation • CHEK2 mutation • MSH2 mutation • MET fusion

TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)

P2, N=12, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed | N=30 --> 12

1 month ago

Trial completion • Enrollment change • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)

CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • FANCF mutation • NBN mutation • FANCG mutation • FANCI mutation • FANCM mutation

Rubraca (rucaparib)

SPORE: A Study of Pembrolizumab and Olaparib for People with Metastatic Pancreatic Ductal Adenocarcinoma and Homologous Recombination Deficiency or Exceptional Treatment Response to Platinum-Based Therapy (clinicaltrials.gov)

P2, N=63, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

1 month ago

Enrollment closed • Metastases

MSK-IMPACT

Keytruda (pembrolizumab) • Lynparza (olaparib)

TBCRC 048: Olaparib in Metastatic Breast Cancer (clinicaltrials.gov)

P2, N=114, Active, not recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

1 month ago

Trial completion date • Trial primary completion date • Metastases

PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • 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) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

BRCA2 mutation • BRCA1 mutation • HR positive • PALB2 mutation • PGR positive • BRCA mutation

Lynparza (olaparib)

Understanding genetic variations associated with familial breast cancer. (PubMed, World J Surg Oncol)

Familial breast cancer has been linked to several genetic diseases and mutations, according to studies. Screening for genetic disorders is recommended by National Comprehensive Cancer Network recommendations. Evaluation of breast cancer candidate variations and risk loci may improve individual risk assessment. Only high- and moderate-risk gene variations have clinical guidelines, whereas low-risk gene variants require additional investigation. With increasing use of NGS technology, more linkage with rare genes is being discovered.

1 month ago

Review • Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)

ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation

Uncovering novel pathogenic variants and pathway mutations in triple-negative breast cancer among the endogamous mizo tribe. (PubMed, Breast Cancer Res Treat)

These findings identified novel variants and key genes contributing to disease development and progression. Further analysis of less studied genes, including RBMX, MRC1, ATM, CTNNB1, and CDKN2A, in TNBC may reveal new potential genes for targeted therapeutic strategies and contribute to clinical advancements in the treatment of TNBC.

1 month ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • RYR1 (Ryanodine Receptor 1) • MRC1 (Mannose Receptor C-Type 1)

TP53 mutation • STK11 mutation • RYR1 mutation

Cohort profile: a nationwide study in Dutch CHEK2 c.1100delC families using the infrastructure of the HEreditary Breast and Ovarian cancer study Netherlands - Hebon-CHEK2. (PubMed, BMJ Open)

Further data linkages with the Netherlands Cancer Registry will allow prospective follow-up and breast cancer risk assessment in unaffected women at the time of genetic testing, risk of contralateral breast cancer and survival in patients with breast cancer. Also, linkage with the nationwide network and registry of histopathology and cytopathology in The Netherlands (PALGA) allows us to retrieve tumour samples to study tumourigenesis.

1 month ago

Journal • BRCA Biomarker

ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2)

ER positive

Inactive Parp2 causes Tp53-dependent lethal anemia by blocking replication-associated nick ligation in erythroblasts. (PubMed, Mol Cell)

Inactive PARP2, but not its active form or absence, impedes Lig1- and Lig3-mediated ligation, causing dose-dependent replication fork collapse, which is detrimental to erythroblasts with ultra-fast forks. This PARylation-dependent structural function of PARP2 at 5'p-nicks explains the detrimental effects of PARP2 inactivation on erythropoiesis, shedding light on PARPi-induced anemia and the selection for TP53/CHK2 loss.

1 month ago

Journal

TP53 (Tumor protein P53) • CHEK2 (Checkpoint kinase 2) • LRIG1 (Leucine Rich Repeats And Immunoglobulin Like Domains 1) • LIG3 (DNA Ligase 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

Detection of Germline Variants in Patients with Localized and Metastatic Prostate Cancer through Guideline-Based Testing. (PubMed, Urol Pract)

In this cohort of patients undergoing guideline-informed germline testing, P/LP germline variants were found in similar proportions across all age ranges and clinical characteristics. Only age at genetic testing for patients with metastatic disease was demonstrated to be predictive of the presence of a P/LP germline variant, highlighting the challenges associated with refining current clinical testing guidelines.

1 month ago

Journal • BRCA Biomarker • Metastases

BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • HOXB13 (Homeobox B13)

PROGRESS: Prostate Cancer Genetic Risk Evaluation and Screening Study (clinicaltrials.gov)

P=N/A, N=400, Recruiting, Massachusetts General Hospital | N=200 --> 400

1 month ago

Enrollment change

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • HOXB13 (Homeobox B13)

CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • PMS2 mutation • NBN mutation

NEDD4L affects stability of the CHEK2/TP53 axis through ubiquitination modification to enhance osteogenic differentiation of periodontal ligament stem cells. (PubMed, Connect Tissue Res)

By contrast, CHEK2 overexpression blocked the osteogenic differentiation of PDLSCs in vitro. This study demonstrates that NEDD4L affects protein stability of the CHEK2/TP53 axis through ubiquitination modification, thus increasing osteogenic differentiation of PDLSCs.

1 month ago

Journal

TP53 (Tumor protein P53) • CHEK2 (Checkpoint kinase 2) • RUNX2 (RUNX Family Transcription Factor 2) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5) • NEDD4 (NEDD4 E3 Ubiquitin Protein Ligase)

Advancing cancer therapy: new frontiers in targeting DNA damage response. (PubMed, Front Pharmacol)

The development of PARP inhibitors like Olaparib has significantly improved the treatment of cancers with DDR defects (e.g., BRCA1 or BRCA2 mutations) based on synthetic lethality...Current research is focused on optimizing these therapies by developing predictive biomarkers for treatment response, analyzing mechanisms of resistance (both intrinsic and acquired), and exploring the potential for combining DDR-targeted therapies with chemotherapy, radiotherapy, and immunotherapy. This article provides an overview of the latest advancements in targeted anti-tumor therapies based on DDR and their implications for future cancer treatment strategies.

1 month ago

Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)

BRCA2 mutation • BRCA1 mutation

Lynparza (olaparib)

Genomic ascertainment of CHEK2 -related cancer predisposition. (PubMed, medRxiv)

Using genomic ascertainment in two population-scale cohorts, this investigation quantified the prevalence, penetrance, cancer phenotype and survival in CHEK2 heterozygotes. Tailored treatment options and surveillance strategies to manage those risks are warranted.

1 month ago

Journal

CHEK2 (Checkpoint kinase 2)

Genetic Profiling of Non-Small Cell Lung Cancer in Moroccan Patients by Targeted Next-Generation Sequencing. (PubMed, Technol Cancer Res Treat)

Our results regarding the proportion of samples with actionable mutations demonstrate the value of NGS testing for NSCLC patients in a real-world clinical diagnostic setting.

1 month ago

Journal • Retrospective data • PD(L)-1 Biomarker • IO biomarker • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CHEK2 (Checkpoint kinase 2)

TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • PTEN mutation • RET mutation • ROS1 fusion • RET rearrangement • ERBB3 mutation • FGFR3 fusion • EGFR mutation + KRAS mutation

Oncomine Precision Assay

2ms

Harnessing the synergy of nanosecond high-power microwave pulses and cisplatin to increase the induction of apoptosis in cancer cells through the activation of ATR/ATM and intrinsic pathways. (PubMed, Free Radic Biol Med)

The obtained results elucidate the cellular mechanisms driving cell apoptosis/death, offering insights for potential advancements in cancer therapy through the combined application of nanosecond pulses of HPM and cisplatin. This serves as a first step for future investigations in this domain.

2 months ago

Journal

BCL2 (B-cell CLL/lymphoma 2) • CHEK2 (Checkpoint kinase 2) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • CASP8 (Caspase 8)

2ms

Homologous recombination deficiency gene panel analysis results in synchronous endometrial and ovarian cancers. (PubMed, Rev Assoc Med Bras (1992))

Pathogenic variations confirming the diagnosis of synchronous endometrial ovarian cancer with genetic alterations were identified in all but one case. ATM gene mutation emerged as the most common alteration and has a potential association with a favorable prognosis.

2 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • 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) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54)

TP53 mutation • HRD • RAD51D mutation • BARD1 mutation • RAD54L mutation • TP53 mutation + ATM mutation

2ms

Distinct landscape and clinical implications of therapy-related clonal hematopoiesis. (PubMed, J Clin Invest)

This Review discusses the potential mechanisms of t-CH development, its mutational landscape, mutant-drug relationships, and its clinical significance. We highlight the distinct nature of t-CH and call for intensified research in this field.

2 months ago

Review • Journal

TP53 (Tumor protein P53) • CHEK2 (Checkpoint kinase 2) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)

TP53 mutation • CHEK2 mutation

2ms

CHEK2 mutation causes manifestations similar to Lynch syndrome and Li-Fraumeni syndrome. (PubMed, Dig Liver Dis)

No abstract available

2 months ago

Journal

CHEK2 (Checkpoint kinase 2)

CHEK2 mutation

2ms

Synchronous Seminoma of Testis and Renal Cell Carcinoma: A Rare Case Report. (PubMed, Medicina (Kaunas))

Chemotherapy with a Bleomycin, Etoposide, and Cisplatin (BEP) regimen was carried out...Treatment with targeted therapy with Sunitinib was started because the risk was favourable according to the Heng criteria... According to the authors, the occurrence of synchronous primary tumours is linked to one's genetic predisposition. DNA sequencing of tumour tissue could provide more information on the corresponding aetiopathogenesis.

2 months ago

Journal

STK11 (Serine/threonine kinase 11) • BAP1 (BRCA1 Associated Protein 1) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)

cisplatin • sunitinib • etoposide IV • bleomycin

2ms

Phospholipase Cδ-4 (PLCδ4) Acts as a Nuclear Player to Influence Cyclin B Expression in the Embryonal Rhabdomyosarcoma Cell Lines RD and A204. (PubMed, Biomolecules)

Our study identifies a novel role for nuclear PLCδ4 as a regulator of cyclin B1 via Akt-dependent phosphorylation. The modulation of PLCδ4 expression and its downstream targets could represent a crucial signaling pathway to block embryonal RMS cell proliferation.

2 months ago

Preclinical • Journal

TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • WNK1 (WNK Lysine Deficient Protein Kinase 1) • AKT1S1 (AKT1 Substrate 1) • CCNB1 (Cyclin B1)

TP53 mutation • MYC amplification • MYC expression • TP53 expression • MYC negative