Initially diagnosed with BRAF V600E-mutated melanoma, he received Dabrafenib and Trametinib...Despite initial treatment with Triptorelin, Docetaxel, and Abiraterone, disease progression occurred...This case illustrates the value of precision medicine and the role of liquid biopsy in guiding immunotherapy decisions for complex oncological cases. It supports the relevance of molecular profiling in selecting effective treatments beyond standard indications.

5 days ago

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

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset)

TP53 mutation • BRAF V600E • TMB-H • BRAF V600 • ATM mutation

Keytruda (pembrolizumab) • Mekinist (trametinib) • Tafinlar (dabrafenib) • docetaxel • abiraterone acetate • triptorelin

11d

Genetic Predisposition to Pancreatic Cancer: A Systematic Review of Hereditary Syndromes and Familial Aggregation. (PubMed, Cancers (Basel))

Identifying high-risk individuals is crucial for effective genetic counseling, testing, and potential screening programs to facilitate early diagnosis and improve outcomes. Future research should prioritize large prospective cohorts, screening programs, and the integration of emerging technologies, such as AI-assisted imaging.

11 days ago

Review • Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

BRCA2 mutation • BRCA1 mutation • ATM mutation • STK11 mutation

13d

Niraparib in Patients With Pancreatic Cancer (clinicaltrials.gov)

P2, N=32, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

13 days ago

Trial completion

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)

13d

Remarkable response to radiation in a non-enhancing diffuse pediatric-type high-grade glioma with germline ATM mutation: The role of PET imaging and integrated histological and molecular analysis. (PubMed, Neurooncol Adv)

The patient received craniospinal radiation with a boost and concurrent temozolomide. She achieved rapid and significant neurologic recovery of function with KPS increasing to 90, accompanied by radiographic improvement. This case highlights the utility of PET/MRI in biopsy planning and underscores the importance of integrated histological and molecular diagnosis for management of non-enhancing gliomas.

13 days ago

Journal

ATM (ATM serine/threonine kinase)

ATM mutation • IDH wild-type

temozolomide

13d

Molecular Genetic Demonstration of the Evolution of Transformed Mycosis Fungoides: A Clinicopathological and Molecular Case Study. (PubMed, J Cutan Pathol)

Many of the mutations described implicate driver mutations in advanced-stage MF and have been associated with poor survival. While there is no evidence suggesting a singular mutation for the pathogenesis of LCT, the constellation of mutations may be responsible for histologic progression to LCT.

13 days ago

Journal

TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CARD11 (Caspase Recruitment Domain Family Member 11) • CDK6 (Cyclin-dependent kinase 6)

TP53 mutation • ATM mutation • TET2 mutation

14d

A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)

P1/2, N=120, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2027 --> Mar 2029 | Trial primary completion date: Mar 2026 --> Mar 2028

14 days ago

Trial completion date • Trial primary 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

berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)

19d

Absence of CD38 Expression in Mantle Cell Lymphoma Correlates with Distinct Pathological and Genetic Features. (PubMed, Hum Pathol)

Biologically, CD38-negative cnMCLs appear to be more likely driven by CD38-independent, alternative signaling pathways. From a clinical perspective, identification of CD38-negative cnMCLs by flow cytometry may help recognizing patients at increased risk for adverse genetic features, including TP53 inactivation.

19 days ago

Journal • IO biomarker

TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • IGH (Immunoglobulin Heavy Locus) • KMT2D (Lysine Methyltransferase 2D) • CD38 (CD38 Molecule) • CD79B (CD79b Molecule) • NOTCH2 (Notch 2) • SOX11 (SRY-Box Transcription Factor 11) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)

TP53 mutation • ATM mutation • IGH mutation

19d

High diffuse bone marrow uptake in 18F-FDG PET/CT may reflect the diverse mutational characteristics of multiple myeloma. (PubMed, Korean J Intern Med)

Patients with high DU showed diverse mutational characteristics, which may reflect the heterogeneous nature of MM and contribute to inferior survival outcomes.

19 days ago

Retrospective data • Journal

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • HUWE1 (HECT UBA And WWE Domain Containing E3 Ubiquitin Protein Ligase 1) • PABPC1 (Poly(A) Binding Protein Cytoplasmic 1)

TP53 mutation • ATM mutation

19d

NCI 9938: M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)

P1, N=66, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

19 days ago

Trial completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation

irinotecan • berzosertib (M6620)

22d

Integrating next-generation sequencing into the routine neuroblastoma workflow identifies actionable genomic alterations and reduces low-yield karyotype testing. (PubMed, Virchows Arch)

We also found that karyotype has limited utility in the setting of NB. Based on this data, we developed an institutional workflow for NB, including MYCN FISH, CMA, and NGS.

22 days ago

Journal • Next-generation sequencing • Tumor mutational burden

TMB (Tumor Mutational Burden) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)

TMB-H • ATM mutation • ALK mutation • MYCN amplification • HRAS mutation

27d

Metastatic Pancreatic Adenocarcinoma with Germline BLM and Somatic ATM Mutations: A Case Report and Review of DNA Damage Response. (PubMed, Ann Case Rep)

The patient was treated with an oxaliplatin-based regimen (mFOLFOX6), modified due to comorbidities, achieving disease stabilization...The presence of pathogenic variants in DNA damage response (DDR) genes (BLM and ATM) suggests a defect in homologous recombination, providing a rationale for platinum-based therapy. We discuss the implications of BLM mutations on therapeutic selection, potential immune checkpoint interactions, and the role of synthetic lethality in management.

27 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BLM (BLM RecQ Like Helicase)

BRCA2 mutation • BRCA1 mutation • ATM mutation

5-fluorouracil • oxaliplatin • leucovorin calcium

DNA Repair gene alterations and efficacy from gemcitabine and nab-paclitaxel with/without durvalumab and tremelimumab in metastatic pancreatic ductal adenocarcinoma. (PubMed, Nat Commun)

Partial response was observed in 7/11 (63.64%) patients with concurrent DNA damage repair gene mutations in the immunotherapy arm. As a prospective study in PDAC identifying a potential biomarker beyond mismatch repair deficiency for benefit from immunotherapy, these data highlight an actionable subgroup of mPDAC.

1 month ago

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

BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase) • FANCA (FA Complementation Group A)

BRCA1 mutation • ATM mutation

Imfinzi (durvalumab) • gemcitabine • albumin-bound paclitaxel • Imjudo (tremelimumab-actl)