TP53 wild-type

Pharmacological inhibition of neddylation with MLN4924 restored P53 levels and reversed the oncogenic effects of CCDC8 both in vitro and in vivo. Together, these findings highlight a novel mechanism of P53 regulation in bladder cancer, position CCDC8 as a potential biomarker and therapeutic target, and suggest a molecular link between chronic bladder inflammation and malignant transformation.

P1, N=119, Active, not recruiting, Boehringer Ingelheim | Trial completion date: May 2026 --> Feb 2026

Three KRAS-mutated tumors also had at least focal mesonephric-like histology. Although rare, p53 wild-type tumors represent a small subset of OCS that show distinct clinical and histologic features and are largely driven by KRAS mutations.

This study provides the first single-cell landscape of de novo TP53-mutated AML, highlighting its reprogrammed leukemic hierarchy and disrupted immune-stromal ecosystem, and offering mechanistic insights and potential therapeutic targets for this high-risk subtype.

These results demonstrate that the integration of optimized nanostructured SERS substrates, Raman spectroscopy, and machine learning constitutes a robust analytical platform for the structural classification of wild-type and mutant p53 proteins. The proposed approach provides a versatile framework for studying conformational changes in biomolecules of biomedical relevance and supports its potential application in cancer biomarker detection and protein misfolding studies.

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.

Additionally, bile acids induce biomolecular condensate formation in mutant p53, sequestering doxorubicin within these structures and suggesting a mechanism for chemoresistance. These findings highlight the role of bile acids in promoting mutant p53 aggregation and therapy resistance, suggesting potential new therapeutic targets for p53 mutant CRC.

In p53-wild-type, PPM1D-mutant DIPG neurospheres (BT869), ATSP-7041 exhibited ~125-fold greater anti-tumor activity than the HDM2-selective antagonist RG7388, consistent with elevated HDMX expression. This feasibility study provides proof-of-concept for on-target p53 reactivation in DIPG using a BBB-penetrant dual HDM2/HDMX inhibitor delivered by the MIND platform. The findings support a translational path for ALRN-6924, the clinical analog of ATSP-7041, in DIPG and potentially other brain tumors that retain wild-type p53 but remain incurable due to drug resistance and restricted CNS access.

Elevated SCD1 levels correlate with increased MYLK4 levels, and their concurrent expression forecasts regorafenib resistance and poor prognosis in colorectal cancer...Patients with colorectal cancer exhibiting elevated MYLK4 activity and wild-type p53 may derive clinical benefits from this combination therapy. These results suggest that MYLK4 may serve as a promising therapeutic target for the treatment of colorectal cancer.

This study supports the hypothesis that the effect of one-carbon nutrient intake on CRC differs according to tumor conditions.

In contrast, R249S mutation resulted in greater water retention, along with the emergence of independent spherical aggregates. These results provide mechanistic insights into how M237I and R249S mutations promote temperature-dependent liquid-liquid phase separation (LLPS) and subsequent aggregation of p53C, suggesting promising avenues for anticancer therapeutic strategies that target phase separation-driven oncogenesis.

CAR-T cell therapy is an effective treatment for CNSL patients harboring TP53 mutations and has the same efficacy as traditional treatment methods. Additionally, CAR-T cells may be more effective for TP53+ CSNL patients with a non-GCB classification.