TP53 wild-type

Combining eprenetapopt with carboplatin shows promising preclinical efficacy by enhancing cytotoxicity in olaparib-resistant models and demonstrating synergistic interaction; these data support the combination as a potential strategy to mitigate PARPi resistance and carboplatin cross-resistance in TP53 mutant HGSOC and TNBC cell lines. Although further studies are needed to elucidate the molecular mechanisms underlying the synergistic effect, here we point out the combination of eprenetapopt and carboplatin as a potential therapeutic strategy to address olaparib resistance in HGSOC and TNBC patients.

Functionally, MV4-11QR cells showed broad cross-resistance to clinically relevant agents, including midostaurin, venetoclax, and cytarabine. Importantly, pharmacological targeting of mutant p53 with eprenetapopt or MAPK signaling with trametinib restored sensitivity to quizartinib, inducing synergistic or additive cytotoxic effects and increased apoptosis. Together, these findings define a multilayered resistance program involving genetic, signaling, and metabolic adaptations and support rational combination strategies to overcome FLT3 inhibitor resistance in AML.

In PDX models, MD-265 was not toxic and prolonged survival. MD-265 is a potent and specific MDM2 degrader with broad pre-clinical activity and a promising drug candidate for the treatment of leukemias.

All patients underwent surgical resection followed by temozolomide-based chemoradiation; two received fotemustine and bevacizumab, and one underwent re-irradiation. EM can arise despite MGMT-promoter methylation in IDH-wildtype GBM. Imaging red flags (high perfusion, surface contact, necrotic/FDG-avid cervical nodes) and clinical cues (axial pain, cytopenias, neck masses) should prompt early systemic staging (CT/PET-CT) and targeted tissue confirmation to advance management.

The CLL-1 targeted NPs loaded with MDP5 and AZA demonstrated superior AML control and targeting of LSCs in TP53-mutant mice models, while sparing normal hematopoiesis in healthy NSG mice. These promising results highlight a potential efficacy of our novel CLL-1 targeted NP combination approach to treat AML, particularly those harboring TP53 mutation.

[18F]1 showed favorable biodistribution characteristics in healthy mice, and preliminary PET/CT imaging studies revealed a higher uptake of [18F]1 in SJSA-1 xenografts compared to muscle at 1 h post-injection. Western blot analysis of SJSA-1 cells and immunohistochemical staining of SJSA-1 tumor sections confirmed high MDM2 expression and its localization in the nuclei of tumor cells, corroborating the PET imaging data.

ITGB4 is a key molecule influencing cisplatin sensitivity in p53 WT BC, and the combination of STAT3 inhibitors can enhance the antitumor effect of cisplatin.

P=N/A, N=82, Not yet recruiting, Hospital Universitari de Bellvitge | Trial completion date: Dec 2026 --> Sep 2028 | Initiation date: May 2026 --> Sep 2026 | Trial primary completion date: Jun 2026 --> May 2027

This IHC-based, biologically informed stratification identifies an occult aggressive subset within luminal tumors and complements routine pathology. The internally validated nomogram is exploratory given cohort composition and lack of external validation; multicenter validation is warranted.

Accurate classification is essential, as prognosis, progression risk, and recurrence rates differ among subgroups. Diagnosis relies on integrated assessment of clinical presentation, histopathology, and immunophenotype, particularly p16 and p53 expression.

These findings establish a mechanistic link between hormonal signaling, p53 allelic status, and m6A-dependent post-transcriptional regulation. Although further in vivo validation is required, disruption of the ALKBH5-REG1A axis may contribute to heterogeneous endometrial responses to tamoxifen, thereby providing a conceptual framework for biomarker-oriented investigation.

P1/2, N=78, Not yet recruiting, University College Dublin