TP53 mutation

Understanding the biology and clinical impact of TP53 mutations is vital for risk stratification and treatment selection. This review summarises the molecular function of p53, the clinical relevance of TP53 mutations in haematological malignancies, and emerging therapeutic approaches.

In this review, we discuss the genetic evolution of CRC and highlight how emerging functional models, including PDOs and organoid-on-a-chip platforms, bridge the gap between genomic alterations and tumor behavior. We propose that integrating these platforms offers a promising framework for advancing functional precision medicine and improving our understanding of CRC biology.

This multinational registry-based analysis highlights evolving global treatment patterns, supports newer TKIs' effectiveness, and identifies clinical and molecular factors associated with treatment duration.

Initial therapy with 'pemetrexed + carboplatin + tislelizumab' was administered...The RA flare was managed with methylprednisolone 1 mg/kg/day followed by a slow prednisone taper and sulfasalazine. Treatment was switched to 'pemetrexed + carboplatin + bevacizumab'...It may create a potential opportunity for conversion surgery in well-responding patients, enabling long-term disease control. This case underscores the critical importance of highly individualized, multidisciplinary treatment decision-making.

Transcriptomic profiling of CD34+ bone marrow cells revealed unique, homogeneous gene expression patterns, particularly within the AML-like, biTET2, SF3B1, and TP53-complex subgroups. Further integration of multi-omics data may refine MDS classification, improving clinical decision-making and guiding the development of targeted therapies.

Targeted next-generation sequencing demonstrated high tumor mutational burden (>10 mutations/Mb) and 2 common driver mutations [TP53 (c.853G>A) and TERT (c.-146C>T)]. This is the first report of an HPV-independent cervical SCC with choriocarcinomatous differentiation, supporting a clonal origin with divergent differentiation, and suggesting comprehensive therapies combining immunotherapy and pathway inhibitors for this aggressive cancer.

The mOS of the EGFR-TP53 co-mutant group who received second-line TKIs combined with platinum-containing double-drug chemotherapy and bevacizumab after the progression of first-line single-drug TKIs was 27.0 months versus 6.0 months compared with those who did not receive second-line therapy (P = .019). In first-line EGFR-TKIs monotherapy in patients with EGFR-TP53 co-mutation, osimertinib was clearly superior to gefitinib. In first-line EGFR-TKIs monotherapy progression, TKIs combined with chemotherapy and antiangiogenesis therapy could prolong patients' survival.

The 4 signature genes showed abnormal expression in HCC tissues at multiple levels. This study identified 2 PRG subtypes and a robust 4-gene prognostic signature for HCC, which accurately predicts prognosis, reflects tumor immune microenvironment features, and guides precision therapy selection, highlighting PRGs' potential as HCC biomarkers and therapeutic targets.

Specific genomic alterations may help stratify immunotherapy outcomes in recurrent or metastatic cervical cancer. The proposed genomic risk model remains exploratory and requires validation in larger, independent cervical cancer cohorts.

Our findings highlight the potential of cisplatin-alpelisib treatment in a subset of HGSOC patients with PIK3CA overexpression, mediated either through gene amplification or transcriptional modulation, reflecting the wider application of alpelisib in PIK3CA-non-mutated ovarian cancer.

RNA-triggered chromatin shredding may offer a new way to attack cancers driven by mutations that have resisted conventional drugs, two new studies show. In mouse models, upon activation by a target transcript, the CRISPR enzyme Cas12a2 can selectively eliminate tumor cells carrying mutations in TP53, MYC, and other hard-to-drug cancer genes.

Our data show that TP53 isoforms are dysregulated in B-ALL at diagnosis as well as at relapse. Short TP53 isoforms, particularly Δ133p53 is associated with better prognosis suggesting its potential role in refining risk stratification of B-ALL.