KRAS (KRAS proto-oncogene GTPase)

P1/2, N=74, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2026 --> Nov 2026 | Trial primary completion date: Apr 2026 --> Oct 2026

BRCA2 is the most common gene with germline variations, while CDK12 is the most frequently mutated gene in somatic HRR variants. This study suggests that HRR gene testing in patients with high-risk HSPC would help identify those with more aggressive clinical features and guide prognostication and potential targeted therapeutic strategies.

BMCRC is challenging because of its rarity and complex management. Recent advances in systemic therapies and diagnostic techniques have improved patient outcomes. Future research should focus on novel therapeutic approaches and biomarker validation to enhance early detection and personalize treatment strategies.

In our cohort, KRAS mutations were more prevalent in PLMAC than PLNMAC (72% vs. 40%, P < 0.05). However, the KRAS G12C variant was significantly less frequent in PLMAC compared to PLNMAC (19% vs. 47%, P < 0.05), suggesting that patients with PLMAC are less likely to benefit from KRAS G12C-targeted therapy. These findings underscore the importance of comprehensive KRAS genotyping and highlight the need for developing additional KRAS variant-targeted therapy for patients with PLMAC.

Oral Lm-based cancer vaccines targeting CRC elicit robust, widely disseminated, and persistent tumor-specific immune responses in mice. These vaccines limit CRC development when administered prophylactically and provide tumor control when administered therapeutically with ICI. Thus, oral delivery of Lm-based cancer vaccines coupled with ICI may provide improved control of CRC progression in clinical application.

Collectively, our results provide a theoretical framework for understanding the complex mechanisms mediating ATBC-induced myocardial damage. They also offer crucial insights for developing preventive and therapeutic strategies targeting cardiac disorders potentially arising from exposure to ATBC-containing plastic products or environmental ATBC contamination.

Multiplex immunofluorescence staining demonstrated that BCL-xL inhibition effectively triggered apoptosis in heterogeneous PDX tumor slice models, including models harboring oncogenic BRAF mutations. Our findings suggest that cetuximab-resistant CRC retains apoptotic competence, and that BCL-xL inhibition serves as a robust alternative therapeutic strategy that is largely independent of the tumor mutational profile.

P3, N=480, Recruiting, University of Campania Luigi Vanvitelli

These data provide an expanded understanding of the molecular underpinnings of EMCG-including the first description of a SMARCA4 frameshift variant in this entity-and demonstrate that while gastrointestinal marker immunoexpression is relatively common among endometrial carcinomas, strictly defined EMCG remains rare (<1%). As awareness of this entity grows, pathologists should take care not to over-interpret gastrointestinal marker expression as stand-alone evidence of an EMCG diagnosis.

Inhibition of MG/Mϕ with long-term minocycline treatment attenuated the incidence of ICHs around bAVMs. Our study indicates that MG/Mϕ are involved in destabilization of KRAS-induced bAVM, leading to hemorrhagic conversion/ICH. Thus, modulation of MG/Mϕ may reduce ICH risk in bAVM patients.

Other immune partners might include vaccines, bispecific antibodies, and cell therapy. A major clinical opportunity eventually would be combining RAS inhibitors and immunotherapy in the adjuvant, neo-adjuvant, and interception settings, provided this new class of drugs is developed keeping its immune modulatory power in mind.

Eighty-three percent of CR-NEC received first-line platinum-etoposide, while 98% of CR-AC patients received first-line fluorouracil-based chemotherapy. Metastatic CR-NEC and CR-AC are clinically distinct, with NEC demonstrating more aggressive features, limited treatment effect, and worse prognosis. Although they share important driver mutations, the underlying reason for their marked clinical differences remains unclear.