News - TP53 mutation - LARVOL VERI

14h

Novel antagonist APG-115 targets MDM2-p53 to induce p53-mediated apoptosis and radiosensitization in colorectal cancer. (PubMed, Clin Exp Med)

APG-115 effectively inhibits proliferation, induces apoptosis, and enhances radiosensitivity in p53 wild-type colorectal cancer. These findings support APG-115 as a promising therapeutic candidate for colorectal cancers retaining functional p53.

14 hours ago

Journal

MDM2 (E3 ubiquitin protein ligase) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • ANXA5 (Annexin A5)

TP53 mutation • TP53 wild-type

alrizomadlin (APG-115)

14h

Ibrutinib in Treating Participants With Untreated High Risk Smoldering Mantle Cell Lymphoma (clinicaltrials.gov)

P2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2026 --> Feb 2028 | Trial primary completion date: Feb 2026 --> Feb 2028

14 hours ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)

TP53 mutation • CD20 positive • TP53 wild-type

Imbruvica (ibrutinib)

22h

RP-6306 in Patients With Advanced Cancer (clinicaltrials.gov)

P2, N=28, Completed, Canadian Cancer Trials Group | Active, not recruiting --> Completed

22 hours ago

Trial completion

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • UGT1A1 (UDP glucuronosyltransferase family 1 member A1) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)

TP53 mutation • KRAS mutation • HER-2 amplification • RAS mutation

Herceptin (trastuzumab) • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium • lunresertib (RP-6306) • camonsertib (RP-3500)

23h

LEAH: Cohort Evaluation of Body Fluids Early Detection of Cancer in High-risk Individuals (clinicaltrials.gov)

P=N/A, N=5909, Not yet recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Initiation date: Jun 2025 --> Feb 2026

23 hours ago

Trial initiation date

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) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • POLE (DNA Polymerase Epsilon) • RUNX1 (RUNX Family Transcription Factor 1) • BAP1 (BRCA1 Associated Protein 1) • ETV6 (ETS Variant Transcription Factor 6) • MLH1 (MutL homolog 1) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • CDH1 (Cadherin 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • RAD51D (RAD51 paralog D) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • DICER1 (Dicer 1 Ribonuclease III) • FLCN (Folliculin) • PRSS1 (Serine Protease 1) • SDHD (Succinate Dehydrogenase Complex Subunit D) • TXNIP (Thioredoxin Interacting Protein) • ANKRD26 (Ankyrin Repeat Domain Containing 26) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • HOXB13 (Homeobox B13)

TP53 mutation • PTEN deletion

Interpretable deep learning model of circulating genomics for quantitative survival prediction in advanced non-small cell lung cancer. (PubMed, Clin Transl Oncol)

The interpretable DeepSurv model, integrating multimodal features, enables quantitative survival prediction and risk stratification in advanced NSCLC, facilitating personalized decision-making.

1 day ago

Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A)

TP53 mutation • EGFR mutation • PIK3CA mutation • ARID1A mutation • STK11 mutation • MET mutation

MSK-ACCESS

Integrated high-resolution copy number and histomolecular analysis of diffuse hemispheric glioma, H3 G34-mutant reveals universal TP53 abnormalities. (PubMed, Brain Pathol)

Collectively, a TP53 abnormality at copy number (12/26, all cnLOH), sequence (55/60) and protein expression (46/48) level was detected in all 60 cases. In conclusion, integrated high-resolution copy number and histomolecular analysis expanded the spectrum of genetic changes associated with DHG-H3 G34, including the presence of universal TP53 abnormalities with frequent cnLOH-a copy number abnormality that has been largely unrecognized-for this new 2021 World Health Organization central nervous system tumor type.

1 day ago

Journal

TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PMS2 (PMS1 protein homolog 2) • ATRX (ATRX Chromatin Remodeler) • H3-3A (H3.3 Histone A) • OLIG2 (Oligodendrocyte Transcription Factor 2)

TP53 mutation

Ultra-deep duplex sequencing reveals unique features of somatic evolution in the normal tissues of a family with Li-Fraumeni syndrome. (PubMed, bioRxiv)

Most somatic TP53 mutations in LFS that could be assessed for phase arose on the chromosomal copy lacking the p.R181H variant. Our study reveals how the germline p.R181H variant reshapes baseline somatic mutation and selection in normal tissues and highlights the importance of understanding early somatic evolution in LFS prior to cancer development and treatment.

1 day ago

Journal

TP53 (Tumor protein P53) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • GATA2 (GATA Binding Protein 2)

TP53 mutation • TET2 mutation

TET2 and TP53 Mutations Cooperatively Modulate the Response to Inflammation to Promote Leukemic Transformation. (PubMed, bioRxiv)

TET2 and TP53 mutations co-operate leading to advanced hematologic malignancy. TET2 mutations promote an inflammatory environment and TP53 mutation supports tolerance to this inflammatory stress.

1 day ago

Journal

TP53 (Tumor protein P53) • TET2 (Tet Methylcytosine Dioxygenase 2)

TP53 mutation • TET2 mutation

Dietary and lifestyle inflammation scores in relation to colon cancer recurrence in subgroups of patients based on common molecular tumour characteristics. (PubMed, ESMO Gastrointest Oncol)

Persons who have a more pro-inflammatory lifestyle may have an increased recurrence risk (IRR 1.21, 95% CI 0.97-1.52), which was most pronounced for persons with MSS and KRAS or PIK3CA wildtype tumours (IRR 1.31, 95% CI 0.90-1.90 and IRR 1.30, 95% CI 0.98-1.71, respectively). Our results suggest that associations between the LIS and recurrence might differ based on molecular tumour characteristics.

1 day ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • APC (APC Regulator Of WNT Signaling Pathway)

TP53 mutation • KRAS mutation • BRAF mutation • PIK3CA mutation • KRAS wild-type

Real-world evidence of chemotherapy effects in advanced pancreatic ductal adenocarcinoma: prognostic significance of TP53 status in gemcitabine plus nab-paclitaxel therapy. (PubMed, ESMO Gastrointest Oncol)

Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) therapies are widely used to treat advanced pancreatic ductal adenocarcinoma (PDAC)...In Japanese real-world data, GnP showed superior TTP compared with FFX for advanced PDAC. TP53 status may serve as a prognostic biomarker in patients receiving GnP therapy.

1 day ago

Journal • HEOR • Real-world evidence

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMAD4 (SMAD family member 4)

TP53 mutation • TP53 wild-type

gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium

Challenging the extended phenotype: HRD-negative salivary gland carcinoma in a BRCA1 founder-variant carrier, case report and literature review. (PubMed, Front Oncol)

Clinical implications are direct: SGTs in BRCA1 carriers should not be assumed eligible for PARP inhibitor therapy without HRD confirmation, and enhanced surveillance appears unwarranted. This case underscores that co-occurrence does not establish causation and highlights the critical importance of functional validation before expanding hereditary cancer spectra.

1 day ago

Journal • BRCA Biomarker • PARP Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)

TP53 mutation • HRD

Tumor microenvironment changes after treatment with avelumab and immune- stimulating agent combinations in patients with advanced solid tumors. (PubMed, Res Sq)

Methods We performed whole exome sequencing (WES), bulk RNAseq, multiplex immunofluorescence (mIF) and chromogenic immunohistochemistry (IHC) on tumor tissue and flow cytometry of the peripheral blood to study longitudinal changes following the combination of avelumab with utomilumab (a 4-1BB agonist) (arm A), PF-04518600 (an OX40 agonist) (arm B), utomilumab and PF-04518600 (arm C) and utomilumab and radiotherapy (arm D) in phase I/II study (NCT03217747). Conclusions Our findings, though limited, highlight genomic differences between histologic subsets and outcome as well as the need for combination strategies that drive the recruitment and/or priming of anti-tumor T cells and address low immune permissive tumor states in patients with advanced solid tumors. Clinical trial registration: This clinical trial was registered on clinicaltrials.gov NCT03217747.

1 day ago

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

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • CCNE1 (Cyclin E1) • IFNG (Interferon, gamma) • TTN (Titin)

TP53 mutation • KRAS mutation • KRAS G12C • KRAS G12D • TMB-L • KRAS G12

Bavencio (avelumab) • utomilumab (PF-05082566) • ivuxolimab (PF-04518600)