TP53 mutation

P=N/A, N=1500, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Dec 2025 --> Dec 2032 | Trial primary completion date: Dec 2025 --> Dec 2030

The observation of immune responses to both vaccine and non-vaccine neoantigens raises the possibility of epitope spreading, though this finding requires cautious interpretation due to pre-existing immune responses. As a single-patient case study, these results remain preliminary and must be validated in larger cohorts.

This study provides the first genomic evidence of shared and divergent somatic mutations in SMARCA4-dNSCLC and its hepatic metastasis. Clonal evolutionary analysis confirmed the diagnosis of SMARCA4-dNSCLC with hepatic metastasis, resolving diagnostic challenges and supporting precision therapy.

Genetic contexts such as BRCA2 loss and mutant p53 further heighten this vulnerability. This review synthesizes mechanistic evidence linking dCK to stress-adaptive nucleotide metabolism, summarizes progress in small-molecule dCK inhibitor development, and highlights dCK inhibitor TRE-515 as the first clinically tested agent, alongside plasma nucleoside profiling and PET imaging as translational pharmacodynamic biomarkers.

Selecting candidates for nonsurgical management of endometrial cancer remains challenging. The association of myometrial invasion to response illustrates the importance of pretreatment imaging. Given non-response in 3 of 4 MMRd and both p53 mutated tumors, molecular testing should be considered in all these patients.

The highest prevalence of L1CAM was found in p53abn endometrial tumors. L1CAM positivity is associated with poor survival outcomes, particularly in MMR-D and NSMP subgroups. These findings highlight the potential of L1CAM as a prognostic biomarker that could refine risk stratification and guide adjuvant management more accurately in endometrial cancer, warranting validation in prospective studies.

This case illustrates the characteristic clinicopathological and molecular features of CMMRD-associated pediatric high-grade glioma and underscores the critical role of routine mismatch repair immunohistochemistry. Integrated histological and genomic evaluation is essential for accurate diagnosis, appropriate genetic counseling, and potential therapeutic implications. Key Points • This case represents a pediatric high-grade glioma arising in the setting of PMS2-related constitutional mismatch repair deficiency (CMMRD). • The tumor exhibited an ultra-hypermutated profile with co-occurring TP53, PIK3CA, PIK3R1, and PTEN mutations. • Loss of PMS2 expression in both tumor and non-neoplastic cells was critical in establishing the diagnosis of CMMRD. • The presence of a developmental venous anomaly may relate to underlying PIK3R1 pathway alterations. • Routine mismatch repair immunohistochemistry is essential in pediatric high-grade gliomas, even in the absence of a family history.

Differential diagnoses include conventional perivascular epithelioid cell tumors and Xp11 translocation renal cell carcinoma. Patients with tumors confined to the kidney usually have a good prognosis after complete surgical resection.

Venetoclax-based regimens, combined venetoclax with either hypomethylating agents or low-dose cytarabine, have markedly improved treatment outcomes in elderly patients with acute myeloid leukemia (AML). Importantly, the combination of bortezomib and venetoclax significantly prolongs the survival of mice inoculated with venetoclax-resistant AML cell line harboring BAX mutations, which are commonly observed in relapsed AML following venetoclax-based regimens and confer resistance to venetoclax by inhibiting BAX-dependent apoptotic pathway. Collectively, this study provides a rationale for venetoclax-bortezomib combination as a potential strategy to overcome venetoclax resistance in certain AML subsets.

The combination of olaparib plus pembrolizumab has promising activity with durable responses in patients with persistent or recurrent CN-H/p53-abnormal endometrial cancer. Molecular biomarkers may be helpful for patient selection in future studies of this combination.

P1, N=22, Recruiting, Richard Stone, MD | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2026 --> Mar 2027

The incidence of TP53 mutations in pediatric B-ALL is approximately 3%, and these cases are frequently accompanied by complex genetic features. Although the response to initial induction therapy is generally favorable, the prognosis becomes poor once relapse occurs, with limited efficacy observed from current salvage strategies.