This study provides a regional molecular profile of advanced CRC in Bulgaria, highlighting a high prevalence of KRAS mutations and dMMR status, while underrepresentation of rare targetable alterations, likely due to limited use of broad molecular profiling. The association between stromal features and MMR status supports their potential role as surrogate markers in settings with constrained testing resources. Findings underscore the urgent need for equitable access to molecular diagnostics and targeted therapies to close the survival gap between Eastern and Western Europe.

1 day ago

Journal

EGFR (Epidermal growth factor receptor) • 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) • NRAS (Neuroblastoma RAS viral oncogene homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • NTRK (Neurotrophic receptor tyrosine kinase)

TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • MSI-H/dMMR • PIK3CA mutation • BRAF V600 • HER-2 mutation • AKT1 mutation

Ventana MMR RxDx Panel • TruSight Tumor 15 Assay

Multiomics analysis identifies the prognostic significance and biological roles of the HNRNP family in lung adenocarcinoma. (PubMed, Discov Oncol)

This study highlights the critical roles of HNRNP family members in LUAD, identifying HNRNPC as a key prognostic biomarker and potential intervention candidate to improve patient outcomes.

1 day ago

Journal

TP53 (Tumor protein P53) • HNRNPC (Heterogeneous Nuclear Ribonucleoprotein C)

TP53 mutation

Radiotherapy enhances M1 macrophage immunogenic activity through IFNs induction and stimulation in TP53-wild type tumors. (PubMed, Cancer Immunol Immunother)

The RT-mediated immunogenic activation was potentially derived from the RT-induced IFNs, which were speculated to contribute to M1 macrophage polarization and immunogenic activity. These results suggest TP53-wild type tumors may be ideal candidates for combining RT and immunotherapy in clinical settings.

1 day ago

Journal • IO biomarker

TP53 (Tumor protein P53) • IFNG (Interferon, gamma) • IFNA1 (Interferon Alpha 1)

TP53 mutation • TP53 wild-type

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.

2 days ago

Journal

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

TP53 mutation • TP53 wild-type

alrizomadlin (APG-115)

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

2 days 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)

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

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

2 days 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)

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

2 days 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.

3 days 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.

3 days 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.

3 days 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.

3 days 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.

3 days 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