DDR

Using publicly available panel sequencing data, we find that ERCC2 wild type (WT) bladder cancer cases that have high levels of this mutational signature respond better to neoadjuvant platinum therapy and have improved overall survival compared to ERCC2 WT cases with low levels of the signature. We also find that other solid tumor types with ERCC2 mutations also show the characteristic mutational signature seen in NER-deficient ERCC2 -mutant bladder cancers, suggesting a novel approach to therapeutically target these ERCC2 -mutant solid tumors beyond bladder cancer.

Tumor profiling also uncovers actionable mutations in oncogenes like RET and VHL, which can be targeted with specific therapies. This review explores the integration of tumor molecular features with germline genetic data to refine diagnosis, risk assessment, and therapeutic strategies in hereditary cancer.

Fatty acid synthase (FASN), the rate limiting enzyme of de novo lipogenesis, is an important regulator of CRC progression, but the FASN inhibitor TVB-2640 showed only modest efficacy in reducing tumor burden in pre-clinical studies, suggesting combination strategies might be required to prolong patient survival. Importantly, combining FASN inhibition with the chemotherapeutic drug irinotecan synergistically decreased xenograft tumor growth and delayed tumor relapse, which was potentiated by the PARP inhibitor olaparib as maintenance treatment. Taken together, this study describes a therapeutic strategy in which FASN inhibitors can be utilized to delay tumor recurrence after chemotherapy, which is a major challenge in patients with CRC.

This case demonstrates that synchronous lung cancers may result from the combined effects of carcinogen-induced field cancerization and DNA repair deficiencies. The identification of PMS2 and ERCC2 alterations provides mechanistic evidence of genetic vulnerability, highlighting the importance of counseling, surveillance, and potential DNA repair-targeted strategies.

Our findings highlight the value of combining dermatological, radiological, and molecular assessments for accurate diagnosis and counseling. The recurrence of the same variant in unrelated families from one region suggests a founder effect.

These cases represent the first definitive report of cranial RIS following glioma chemoradiation therapy in patients with LFS. The short latency and aggressive nature of these tumors at the irradiated site highlight the need for proactive follow-up in patients with LFS after chemoradiation therapy to screen for RIS and improve outcomes through timely intervention. https://thejns.org/doi/10.3171/CASE25588.

We identified RNA polymerase I transcription and rRNA maturation defects, a highly phosphorylated eukaryotic initiation factor 2 alpha (eIF2alpha), and a shift from cap- to internal ribosomal entry site (IRES) translation, indicating an activated integrated stress response in CS. Disturbances in ribosomal biogenesis and translational control might thus contribute to the development of CS.

Somatic and germline mutations in FANCC occur in an exceedingly small subset of clinically advanced RT but at similar rate to other cancers, and genomic landscape does not appear to be different from RT with wild-type FANCC. Germline testing is warranted, as we see high frequency of germline FANCC mutations.

The infection further impairs host defenses by disrupting tumor suppressor pathways such as p53, dysregulating immune signaling of NF-κB and JAK/STAT, which results in immune evasion through arginine depletion and impaired antigen presentation. By elucidating the coordinated interplay among virulence factors, DNA damage response impairment, and immune modulation, this review highlights potential intervention nodes that may help disrupt persistent infection and ultimately reduce the risk of H. pylori-associated gastric cancer.

Currently, olaparib is approved as maintenance therapy for BRCA1/2-mutated HGSC, and niraparib is approved for platinum-sensitive recurrent disease. Overall, first-line carboplatin treatment remains ideal, yet there may be select utility for PARPi prior to chemotherapy. Using patient-derived tumor models such as spheroids and organoids may provide insights for on-going and future clinical trials to enhance therapeutic outcomes for HGSC patients.

pPOLE have been incorporated into treatment guidelines for several malignancies and are an important predictor of immunotherapy response. This study provides biological insight to guide classification and clinical management of patients with tumors harboring pPOLE.

Post-treatment analyses confirmed mitochondrial depolarization, downregulation of DNA replication, cytokine upregulation, and immune cell infiltration in tumor. These findings highlight the potential of mitochondria-targeted gene therapy combined with chemotherapy as a powerful and innovative strategy for TNBC treatment.