News - MYC amplification

21d

Clear Cell Adenocarcinoma of the Urinary Tract Primary to the Renal Pelvis: A Multi-institutional Clinicopathologic and Molecular Study of Five Patients. (PubMed, Am J Surg Pathol)

Next-generation sequencing analysis of all 5 CCAs revealed mutations within genes implicated in DNA damage repair and chromatin remodeling pathways, including ATM, BRCA1, BRCA2, ARID1A, DICER1, SMAD4, NOTCH1, and MYC amplification. These molecular findings underscore the dysregulation of fundamental cellular processes essential for genomic integrity maintenance.

21 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • SMAD4 (SMAD family member 4) • TFE3 (Transcription Factor Binding To IGHM Enhancer 3) • DICER1 (Dicer 1 Ribonuclease III) • NAPSA (Napsin A Aspartic Peptidase) • PAX8 (Paired box 8) • TFEB (Transcription Factor EB 2)

MYC amplification

21d

Amplification of MYC and Its Enhancer Correlates With Genetic Ancestry in Lung Squamous Cell Carcinoma. (PubMed, JCO Precis Oncol)

Together, our data suggest that ancestry may influence amplification of not only MYC but also its enhancer in LUSC. They also suggest a role for genetic ancestry in chr8q aneuploidy in cancer. These studies further define and expand patients who may benefit from future anti-MYC therapeutic approaches.

21 days ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog)

MYC amplification • MYC expression

23d

Modeling NK-cell lymphoma in mice reveals its cell-of-origin and microenvironmental changes and identifies therapeutic targets. (PubMed, Nat Commun)

Furthermore, targeting KLRG1 alone or combined with MYC inhibition using an eIF4 inhibitor is effective against NK-cell tumors. Therefore, our observations provide insights into the pathogenesis and highlight potential therapeutic targets, including CXCL16, KLRG1, and MYC, in ENKTCL, which can help improve its diagnostic and therapeutic strategies.

23 days ago

Preclinical • Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • IFNG (Interferon, gamma) • CXCR6 (C-X-C Motif Chemokine Receptor 6) • KLRG1 (Killer Cell Lectin Like Receptor G1)

MYC amplification • KLRG1 expression

MYC-dependent upregulation of the de novo serine and glycine synthesis pathway is a targetable metabolic vulnerability in group 3 medulloblastoma. (PubMed, Neuro Oncol)

Our findings support a MYC-induced dependency on the serine/glycine pathway in MBGRP3 that represents a novel therapeutic treatment strategy for this poor prognosis disease group.

1 month ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PHGDH (Phosphoglycerate Dehydrogenase)

MYC amplification • MYC overexpression • MYC expression

Phase II Trial of Gemcitabine and nab-Paclitaxel for Recurrent Osteosarcoma with Serial Monitoring Using Liquid Biopsy: A Report from the National Pediatric Cancer Foundation. (PubMed, Clin Cancer Res)

Gemcitabine and nab-paclitaxel demonstrated similar clinical activity and toxicity compared to previous retrospective reports utilizing gemcitabine and docetaxel in patients with recurrent osteosarcoma. Serial analysis of CTC and ctDNA was feasible in this prospective multi-institution study and provides preliminary data on the use of these assays in patients with relapsed disease.

1 month ago

P2 data • Journal • Liquid biopsy • Biopsy

MYC (V-myc avian myelocytomatosis viral oncogene homolog)

MYC amplification

gemcitabine • docetaxel • albumin-bound paclitaxel

2ms

Ablation of hematopoietic stem cell derived adipocytes reduces tumor burden in syngeneic mouse models of high-grade serous carcinoma. (PubMed, bioRxiv)

Compared to HSCDA Proficient mice, tumors from HSCDA Deficient mice showed reduced densities of dendritic cells (DC) and natural killer (NK) cells, as well as fewer DCs, NKs, and B-cells in proximity to tumor cells, as determined by spatial analysis. Overall, our data suggest that HSCDAs promote HGSC survival and plasticity while downregulating expression of tumor suppressors and altering the peritoneal immune and metabolic environment to promote HGSC progression.

2 months ago

Preclinical • Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • CASP3 (Caspase 3)

MYC amplification • BRCA wild-type • HRAS wild-type

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

6ms

Luminal androgen receptor subtype and tumor-infiltrating lymphocytes groups based on triple-negative breast cancer molecular subclassification. (PubMed, Sci Rep)

The LAR subtype was characterized by a high rate of PIK3CA mutation, CD274 (encodes PD-L1) and PDCD1LG2 (encodes PD-L2) deletion, and a low homologous recombination deficiency (HRD) score. The non-LAR LD TIL group was characterized by a high frequency of NOTCH2 and MYC amplification and a high HRD score.

6 months ago

Journal • Tumor-infiltrating lymphocyte • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AR (Androgen receptor) • HRD (Homologous Recombination Deficiency) • NOTCH2 (Notch 2) • PD-L2 (Programmed Cell Death 1 Ligand 2)

PIK3CA mutation • HRD • MYC amplification • PD-L2 deletion • High HRD score • PD-L1 mutation

6ms

Clinicopathologic and molecular correlates to neoadjuvant chemotherapy-induced pathologic response in breast angiosarcoma. (PubMed, Genes Chromosomes Cancer)

However, NACT patients with MYC-amplified tumors showed better disease-free survival (p = 0.04) compared to MYC-amplified patients without NACT. The overall survival of NACT group correlated with size >10 cm (p = 0.02), pathologic response (p = 0.04), and multifocality (p = 0.01) by univariate, while only size >10 cm (p = 0.03) remained significant by multivariate analysis.

6 months ago

Journal

TMB (Tumor Mutational Burden) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • KDR (Kinase insert domain receptor)

MYC amplification • KDR mutation

7ms

Discovery of a long half-life AURKA inhibitor to treat MYC-amplified solid tumors as a monotherapy and in combination with everolimus. (PubMed, Mol Cancer Ther)

Aurora kinase inhibitors such as alisertib can destabilize MYC-family oncoproteins and have demonstrated compelling anti-tumor efficacy. Furthermore, DBPR728 was found to synergize with the mTOR inhibitor everolimus to suppress c-MYC- or N-MYC- driven SCLC. Collectively, these results suggest DBPR728 has the potential to treat cancers overexpressing c-MYC- and/or N-MYC.

7 months ago

Journal • Combination therapy

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)

MYC amplification • MYC overexpression • MYC expression

everolimus • alisertib (MLN8237)

8ms

Prognostic genomic alterations in patients undergoing liver resection for hepatocellular carcinoma. (PubMed, Mol Biol Rep)

MYC amplifications had a prognostic influence on survival, whereas ARID1AÂ gene mutations were correlated with microvascular invasion. These may serve as prognostic biomarkers and should be validated in large, independent cohort.

8 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A)

ARID1A mutation • MYC amplification

TruSight Oncology 500 Assay

8ms

Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers. (PubMed, Clin Cancer Res)

sWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.

8 months ago

Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 mutation • HRD • MYC amplification • CCNE1 amplification • HRD + BRCA1 mutation • HRD signature

8ms

Genetic sequencing and Novel Therapeutic Targets in Perianal Extramammary Paget Disease (EADO 2024)

We identified MYC amplification and ERBB3 as possible predictors of disease metastases and recurrence. Additional research regarding targetable MYC and ERBB3 therapies are warranted.

8 months ago

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)

TP53 mutation • HER-2 mutation • MYC amplification • ERBB3 mutation

MSK-IMPACT

8ms

Patient-derived tumoroid models of pulmonary large-cell neuroendocrine carcinoma: A promising tool for personalized medicine and developing novel therapeutic strategies. (PubMed, Cancer Lett)

These results highlight the value of preclinical tumoroid models in understanding the pathogenesis of rare cancers and developing treatments. LCNEC showed a high success rate in tumoroid establishment, indicating its potential application in personalized medicine.

8 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AURKA (Aurora kinase A)

MYC amplification

9ms

MYC induces CDK4/6 inhibitors resistance by promoting pRB1 degradation. (PubMed, Nat Commun)

The combination of CDK4/6i and A80.2HCl result in marked regression in tumor growth in vivo. Altogether, these results reveal the molecular mechanisms underlying MYC-induced resistance to CDK4/6i and suggest the utilization of the MYC degrading molecule A80.2HCl to potentiate the therapeutic efficacy of CDK4/6i.

9 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1)

MYC amplification • MYC expression

9ms

Molecular profiling and the impact of treatment on outcomes in adenoid cystic carcinoma (ACC) type-I and II. (PubMed, Clin Cancer Res)

We confirmed the previously reported associations with MYC and TP63 in the prognostically relevant subgroups of ACC-I and II, respectively, and report immunologic differences among these subtypes. Survival outcomes are comparatively worse in ACC-I regardless of treatment type.

9 months ago

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

PD-L1 (Programmed death ligand 1) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NOTCH1 (Notch 1) • TP63 (Tumor protein 63)

MYC amplification • MYC expression

9ms

Complexity of the Genetic Background of Oncogenesis in Ovarian Cancer-Genetic Instability and Clinical Implications. (PubMed, Cells)

Ongoing research shows promise for advancing personalized treatments and refining genetic testing in neoplastic diseases, including ovarian cancer. Clinical genetic screening tests can identify women at increased risk, guiding predictive cancer risk-reducing surgery.

9 months ago

Review • Journal • BRCA Biomarker • PARP Biomarker

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • 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) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • BRAF mutation • PIK3CA mutation • TP53 wild-type • PTEN mutation • ARID1A mutation • MYC amplification

9ms

Acquired Cross-resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC paralogs. (PubMed, Cancer Discov)

Each model was tested in vivo against three clinical regimens: cisplatin plus etoposide, olaparib plus temozolomide, and topotecan. Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC, and this was corroborated in tumor biopsies from relapsed patients. We conclude that ecDNAs with MYC paralogs are recurrent drivers of cross-resistance in SCLC.

9 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog)

MYC amplification

Lynparza (olaparib) • cisplatin • temozolomide • etoposide IV • topotecan

9ms

Retroperitoneal Sarcomatoid Yolk Sac Tumor in a Chemotherapy-Naive Patient With Testicular Postpubertal Type Teratoma: A Rare Case Report With Emphasis on Molecular Features. (PubMed, Int J Surg Pathol)

Therefore, relevant clinicoradiologic information and ancillary work up, including immunohistochemistry and molecular studies, may be helpful for the accurate classification. Our tumor further raises awareness of this rare event, expands the spectrum of its clinical presentation, and explores the molecular features.

9 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • GPC3 (Glypican 3) • ARAF (A-Raf Proto-Oncogene) • SALL4 (Spalt Like Transcription Factor 4)

MYC amplification

9ms

Potential predictive biomarkers for response to immunotherapy in breast angiosarcoma (Sarcoma-RC 2024)

Our prelimary data suggest that sAS discloses an immunosuppressive environment; therefore, compared to pAS, sAS might be a better candidate to immunotherapy.

9 months ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD8 (cluster of differentiation 8) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • FOXP3 (Forkhead Box P3) • ITGAE (Integrin Subunit Alpha E)

MYC amplification

Idylla™ MSI Test

9ms

Genomic Variability Within Intrinsic Subtypes of Advanced Breast Cancer (USCAP 2024)

There is a great genomic variability in each intrinsic subtype of advanced BC, with apparently no genomic pattern correlating with each phenotype. Although a transcriptomic test (Prosigna) can help in the classification of the tumors, NGS sequencing with an extended panel allows identifying genetic variants that might benefit the patient with a targeted therapy i a significant percentage of cases.

9 months ago

BRCA Biomarker • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SF3B1 (Splicing Factor 3b Subunit 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • FGF3 (Fibroblast growth factor 3)

HER-2 negative • PTEN mutation • MYC amplification • CCND1 amplification • AKT1 mutation • TP53 amplification

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

9ms

Development of a high-throughput screening platform to identify new therapeutic agents for Medulloblastoma Group 3. (PubMed, SLAS Discov)

Results showed 8 active compounds, targeting MB reported targets and several are currently approved or in clinical trials for pediatric patients with PBTs, including MB. Moreover, hits were combined to avoid tumor resistance, identifying 3 synergistic pairs, one of which is currently under clinical study for recurrent MB and other PBTs.

9 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog)

MYC amplification

9ms

Prostate Cancer Liver Metastasis: An Ominous Metastatic Site in Need of Distinct Management Strategies. (PubMed, J Clin Med)

Additional risk factors comprised elevated serum AST, LDH or ALP, decreased Hb, genetic markers like RB1 and PTEN loss, PIK3CB and MYC amplification, as well as numerous PC treatments either acting directly or indirectly through inducing liver injury. Further research regarding predictive factors, early detection strategies, and targeted therapies for PCLM are critical for improving patient outcomes.

9 months ago

Review • Journal • Metastases

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta)

MYC amplification

10ms

Marinopyrrole derivative MP1 as a novel anti-cancer agent in group 3 MYC-amplified Medulloblastoma. (PubMed, J Exp Clin Cancer Res)

These preclinical findings highlight the promise of marinopyrrole MP1 as a novel MYC inhibition approach for MYC-amplified MB.

10 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog)

MYC amplification • MYC overexpression • MYC expression

Torisel (temsirolimus)

11ms

Targeting ST8SIA6-AS1 counteracts KRAS inhibitor resistance through abolishing the reciprocal activation of PLK1/c-Myc signaling. (PubMed, Exp Hematol Oncol)

Our study deciphers that the axis of ST8SIA6-AS1/PLK1/c-Myc confers both intrinsic and acquired resistance to KRASi and represents a promising therapeutic target for combination strategies with KRASi in the treatment of KRAS-mutant cancers.

11 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AURKA (Aurora kinase A) • PLK1 (Polo Like Kinase 1)

KRAS mutation • MYC amplification • MYC expression

Lumakras (sotorasib) • Krazati (adagrasib)

11ms

WNT-activated, MYC-amplified medulloblastoma displaying intratumoural heterogeneity. (PubMed, Neuropathol Appl Neurobiol)

No abstract available

11 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog)

MYC amplification

11ms

A Study of PRT2527 in Participants With Advanced Solid Tumors (clinicaltrials.gov)

P1, N=30, Completed, Prelude Therapeutics | Active, not recruiting --> Completed

11 months ago

Trial completion • Trial completion date • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)

HR positive • HER-2 negative • MYC amplification

PRT2527

11ms

Evaluation of a real-world clinico-genomics database of patients with upper gastrointestinal (GI) malignancies in Japan. (ASCO-GI 2024)

As part of a nationwide cancer genome screening project, J-SCRUM GI SCREEN database provides comprehensive genomic information for Asian population (Japan). The prevalence of key actionable gene alterations in each tumor type was highly comparable between J-SCRUM GI-SCREEN and TCGA data.

11 months ago

Clinical • Real-world evidence • BRCA Biomarker • Genomic data • Real-world

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)

TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • HER-2 amplification • PIK3CA mutation • MET amplification • KRAS G12D • ATM mutation • KRAS G12V • MYC amplification • CDKN2A mutation • ATM deletion • KRAS G12 • NFE2L2 mutation • KRAS deletion

12ms

The genomic and immune landscapes of gastric cancer and their correlations with HER2 amplification and PD-L1 expression. (PubMed, Cancer Med)

The combination of HER2 amplification and PD-L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions.

12 months ago

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

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • CDH1 (Cadherin 1)

PD-L1 expression • TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 expression • ARID1A mutation • MYC amplification • PD-L1 amplification • HER-2 amplification + PD-L1 expression • CCNE1 mutation

12ms

Sequential activation of E2F via Rb degradation and c-Myc drives resistance to CDK4/6 inhibitors in breast cancer. (PubMed, Cell Rep)

Our analysis of pre-treatment tumor samples reveals a strong correlation between c-Myc levels, rather than Rb levels, and poor therapeutic outcomes after CDK4/6i treatment. Moreover, we propose that proteasome inhibitors can potentially reverse CDK4/6i resistance by restoring Rb levels.

12 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog)

HR positive • MYC amplification

12ms

Selective inhibition of CDK9 in triple negative breast cancer. (PubMed, Oncogene)

Orally administered CDDD11-8 also inhibited growth of mammary intraductal TNBC xenograft tumours with no overt toxicity in vivo (mice) or ex vivo (human breast tissues). In conclusion, our studies indicate that CDK9 is a viable therapeutic target in TNBC and that CDDD11-8, a novel selective CDK9 inhibitor, has efficacy in TNBC without apparent toxicity to normal tissues.

12 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDK9 (Cyclin Dependent Kinase 9)

MYC amplification

CDDD11-8

12ms

Protocol for mapping the metabolome and lipidome of medulloblastoma cells using liquid chromatography-mass spectrometry. (PubMed, STAR Protoc)

Finally, we detail strategies for metabolite identification and data analysis. For complete details on the use and execution of this protocol, please refer to Gwynne et al..

12 months ago

Journal

MYC (V-myc avian myelocytomatosis viral oncogene homolog)

MYC amplification

12ms

The Molecular, Immunologic, and Clinicodemographic Landscape of MYC-Amplified Advanced Prostate Cancer. (PubMed, Clin Genitourin Cancer)

MYC defines a biologically distinct subset of PCa patients and is characterized with multiple proxies of advanced disease. These data suggest that MYC may be prognostic; independent cohorts are needed to validate these findings.

12 months ago

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

PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CCND1 (Cyclin D1) • FGF3 (Fibroblast growth factor 3) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • RAD21 (RAD21 Cohesin Complex Component) • ZNF703 (Zinc Finger Protein 703)

PD-L1 expression • MSI-H/dMMR • MYC amplification • CCND1 amplification

12ms

Tumor sequencing of African ancestry reveals differences in clinically relevant alterations across common cancers. (PubMed, Cancer Cell)

Interestingly, in lung cancer, KRAS mutations are less common in both smokers and non-smokers with AFR ancestry, whereas the association of TP53 mutations with AFR ancestry is only seen in smokers, suggesting an ancestry-environment interaction that modifies driver rates. Our study highlights the need to increase representation of patients with AFR ancestry in drug development and biomarker discovery.

12 months ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

TP53 mutation • KRAS mutation • KRAS G12C • EGFR L858R • MYC amplification • ROS1 fusion • KRAS G12

1year

Sidedness-Dependent Prognostic Impact of Gene Alterations in Metastatic Colorectal Cancer in the Nationwide Cancer Genome Screening Project in Japan (SCRUM-Japan GI-SCREEN). (PubMed, Cancers (Basel))

The NOTCH3 sole variant was an independent and favorable prognostic factor for left-sided CRC (p < 0.01). The prognostic significance of gene alterations differed between left-sided CRC and right-sided CC.

1 year ago

Journal • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NOTCH1 (Notch 1) • NOTCH3 (Notch Receptor 3)

BRAF V600E • BRAF V600 • MYC amplification • KRAS wild-type • RAS wild-type

1year

Synergistic efficacy of Y box binding protein 1 (YBX1) inhibition combined with chemotherapy for the treatment of MYC-amplified medulloblastoma (SNO 2023)

We identify that combining YBX1 inhibition sensitizes to both gemcitabine and vincristine in vitro and in vivo. We are currently evaluating this YBX1 inhibitor in an “anchor-probe” screen combining with all currently FDA approved drugs. Our findings impart an alluring prospect of targeting YBX1 in combination with chemotherapy, and possibly other compounds could improve patients’ outcomes.

1 year ago

Clinical

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • YBX1 (Y-Box Binding Protein 1)

MYC amplification

gemcitabine • vincristine

1year

Class I HDAC inhibition reduces DNA damage repair capacity of MYC-amplified medulloblastoma cells. (PubMed, J Neurooncol)

Our study identifies the combination of entinostat with olaparib as a new potential therapeutic approach for MYC-driven Group 3 MB.

1 year ago

Journal • PARP Biomarker

MYC (V-myc avian myelocytomatosis viral oncogene homolog)

MYC amplification

Lynparza (olaparib) • doxorubicin hydrochloride • Kisqali (ribociclib) • Xpovio (selinexor) • Partruvix (pamiparib) • idasanutlin (RG7388) • Jingzhuda (entinostat) • vinblastine

1year

GENOMIC ALTERATION BEFORE AND AFTER PROGRESSION ON FIRST EXPOSURE TO PARP INHIBITOR (PARPI) AMONG OVARIAN CANCER PATIENTS (IGCS 2023)

10 patients were platinum sensitive and 10 patients were platinum resistant. The histological type was identified as High grade serous carcinoma at 90% and endometrioid carcinoma at 10%. LOH score increased in 15 patients (88%).

1 year ago

Clinical • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog)

MYC amplification

1year

Molecular heterogeneity and co-altered genes in MET-amplified ALK-positive lung cancer: Implications for MET targeted therapy. (PubMed, Lung Cancer)

MET-amplified, ALK + NSCLC often presents with high-level and heterogeneous amplification in tissue, seldom overlaps with ALK mutations, and frequently co-occurs with alterations associated with aggressive tumor biology.

1 year ago

Journal

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • EML4 (EMAP Like 4)

TP53 mutation • EGFR mutation • ALK positive • MET amplification • EGFR amplification • ALK rearrangement • MYC amplification • MET mutation • ALK amplification • EML4-ALK variant 1

1year

Longitudinal NGS diagnostics of sAML under therapy with CPX351 - clonal dynamics under selection pressure (DGHO 2023)

Genetic aberrations classified as high-risk by the ELN recommendations such as mutations in ASXL1 and RUNX1 were not associated with a significantly worse response rate. On the contrary and as expected, mutations in TP53 showed the worst response rate.

1 year ago

Next-generation sequencing

TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1)

TP53 mutation • MYC amplification • ASXL1 mutation

Vyxeos (cytarabine/daunorubicin liposomal formulation)