TP53 wild-type

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.

These effects are associated with the downregulation of key cell cycle regulators, including CCNA2/B1 and CHEK1. Together, these findings highlight the potential of Linarin as a promising therapeutic option for NSCLC.

Together, these findings identify VDAC1 as a direct p53 target whose expression, oligomerization, and pro-apoptotic activity are regulated by p53. They also reinforce the central role of VDAC1 oligomerization in apoptosis.

SAHA imposes a common anti-proliferative core but engages distinct lineage-conditioned risk modules in LUAD and LUSC-cell-cycle/migration-linked in LUAD and checkpoint/stress-linked in LUSC. These SAHA feature-sensing modules provide a mechanistic and clinically anchored framework for subtype-tailored HDAC-directed combinations and for future development of HDACi-aligned biomarkers in NSCLC.

MLH1 loss identifies a subset of MMRd ECs with worse outcomes and lower CD8+ densities supporting substratification of this molecular subtype. Grade, histotype, ER, PR, L1CAM, CTNNB1 and p53 status do not add prognostic refinement within MMRd EC.

The 4-year survival of AML with defective MDM2 inhibitor induced TP53-mediated apoptosis despite WT TP53 was dismal at 19% when NPM1 was co-mutated and 6% when NPM1 was WT. In summary, we identified prevalent multi-causal defects in TP53-mediated apoptosis in AML resulting in extremely poor patient survival.

In summary, dynamic reassessment with IPSS-M prior to alloHSCT offers no prognostic advantage over baseline evaluation at diagnosis in HMA-treated MDS patients. Accordingly, risk reduction should not be regarded as a therapeutic goal or trial endpoint, whereas risk progression constitutes an adverse marker that may inform incorporation of post-transplant maintenance strategies or intensified conditioning regimens to improve survival.

Increased awareness and documentation of CHEC are essential to refining diagnostic criteria, informing prognosis, and optimizing patient management. Future studies are needed to further characterize the molecular landscape and clinical behavior of this rare entity.