Patients with mCRPC harboring effector HRR mutations derive greater clinical benefit from PARPi plus ARSi than those with sensor mutations. These findings highlight the heterogeneous predictive value of HRR gene alterations and suggest that mutation sub-class should guide treatment decisions in HRD-positive mCRPC.

3 months ago

Clinical data • Journal • BRCA Biomarker • PARP Biomarker

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) • CHEK1 (Checkpoint kinase 1) • FANCD2 (FA Complementation Group D2)

HRD • PALB2 mutation • CHEK2 mutation • CHEK1 mutation

Lynparza (olaparib) • abiraterone acetate

5ms

Aberrant splicing of CHEK1 is a driver of megakaryocytic dysplasia in U2AF1S34F mutant myelodysplastic neoplasms. (PubMed, Leukemia)

Accordingly, treatment with selective CHK1 inhibitor significantly reduces abnormal MK production in vitro. Taken together, these findings demonstrate that U2AF1 mutations induce the generation of abnormal MKs by driving aberrant splicing of the CHEK1 cell cycle-related gene, revealing the molecular basis for dysmegakaryopoiesis in MDS and identifying a new potential target for MDS treatment.

5 months ago

Journal

U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CHEK1 (Checkpoint kinase 1)

CHEK1 mutation

5ms

Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer (clinicaltrials.gov)

P1/2, N=71, Recruiting, Yonsei University | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

5 months ago

Trial completion date • Trial primary completion date • Checkpoint inhibition

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • 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)

HER-2 positive • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation

Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel

6ms

Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)

P2, N=51, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2025 --> May 2026

6 months ago

Trial 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)

ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation

Lynparza (olaparib)

6ms

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 | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

6 months ago

Trial completion date • Trial primary completion 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)

ATM mutation • PALB2 mutation • CHEK2 mutation • CHEK1 mutation

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 2026 --> Mar 2028 | Trial primary completion date: Mar 2025 --> Mar 2027

9 months ago

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)

ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation

Lynparza (olaparib)

9ms

Profiling genetic mutations in the DNA damage repair genes of oral squamous cell carcinoma patients from Pakistan. (PubMed, Sci Rep)

TP53p.P33R was predominantly associated with moderately differentiated tumors (84.60%), naswar users (86.60%) and positive family history of cancer (91.60%). The TP53p.P33R, ATRp.M211T and CHEK1p.I437V mutations were found recurrently in 21/27 (77.7%), 20/27 (74.04%), and 27/27 (100%) patients, suggesting its potential biomarker applications in local screening.

9 months ago

Journal

TP53 (Tumor protein P53) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1)

TP53 mutation • ATM mutation • CHEK2 mutation • CHEK1 mutation

11ms

Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer (clinicaltrials.gov)

P1/2, N=71, Recruiting, Yonsei University | Not yet recruiting --> Recruiting | Trial completion date: May 2023 --> May 2025 | Trial primary completion date: Dec 2022 --> Dec 2024

11 months ago

Enrollment open • Trial completion date • Trial primary completion date

HER-2 positive • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression

Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel

12ms

Altered TP53, CDKN2A, ATM, EPHA7, POT1, CHEK1, GRIN2A, and EGFR Predict Shorter Survival in Penile Squamous Cell Carcinoma. (PubMed, Mod Pathol)

We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular-pathological, clinical, and prognostic analysis correlating with prognosis.

12 months ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • KMT2D (Lysine Methyltransferase 2D) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • FAT1 (FAT atypical cadherin 1) • CHEK1 (Checkpoint kinase 1) • CASP8 (Caspase 8) • EPHA3 (EPH receptor A3) • GRIN2A (Glutamate Ionotropic Receptor NMDA Type Subunit 2A) • POT1 (Protection of telomeres 1) • EPHA7 (EPH Receptor A7)

PD-L1 expression • TP53 mutation • TMB-H • PIK3CA mutation • PD-L1 negative • TMB-L • KMT2D mutation • HRAS mutation • TP53 expression • CHEK1 mutation • GRIN2A mutation • CHEK1 expression

12ms

Response to Carboplatin and Paclitaxel in the treatment of hereditary breast ovarian cancer syndrome (HBOC): a case report. (PubMed, J Pak Med Assoc)

This dynamic treatment not only led to nearly complete remission of high-grade ovarian serous cancer but also triggered regression in grade-2 invasive ductal breast cancer after just a few rounds of chemotherapy. Consequently, what started as palliative care evolved into a curative triumph.

12 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CHEK1 mutation • CHEK1 expression

carboplatin • paclitaxel

1year

Identifying Novel Germline Mutations and Copy Number Variations in Patients With SCLC. (PubMed, JTO Clin Res Rep)

Patients with SCLC with the seven pathogenic alterations were observed to have a numerically longer overall survival (hazard ratio = 0.50) and progression-free survival (hazard ratio = 0.45) though not statistically significant compared with the remaining cohort. Our study identifies novel germline alterations, including a CNV, and provides additional evidence that germline factors could be important contributing factors to the development of SCLC.

1 year ago

Journal

SLFN11 (Schlafen Family Member 11) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BBC3 (BCL2 Binding Component 3) • BCORL1 (BCL6 Corepressor Like 1) • FANCC (FA Complementation Group C)

BRIP1 mutation • CHEK1 mutation • CHEK1 expression

1year

CHANGEABLE: Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer (clinicaltrials.gov)

P2, N=37, Completed, Fudan University | Recruiting --> Completed

1 year ago

Trial completion • Metastases

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)

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

Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)