KRAS (KRAS proto-oncogene GTPase)

P1/2, N=36, Terminated, SignalChem Lifesciences Corporation | N=92 --> 36 | Trial completion date: Sep 2028 --> Dec 2025 | Recruiting --> Terminated | Trial primary completion date: Sep 2026 --> Dec 2025; Lack of efficacy and enrollment challenges

Notably, NPM1 expression correlates with elevated WNT signaling and proliferation in human colorectal cancer (CRC), while CRCs harboring NPM1 deletions exhibit preferential TP53 inactivation, underscoring the clinical relevance of our findings. Being dispensable for adult epithelial homeostasis, NPM1 represents a promising therapeutic target in p53-proficient WNT-driven tumors, including treatment-refractory KRAS-mutant CRC, and hepatic cancers.

In contrast, specific inhibition of KRAS induced modest enhancement of EGFR activity and SASP in a JNK-independent manner. Collectively, our study proposes that the CDK4/6 inhibitor may achieve greater therapeutic efficacy when combined with the EGFR inhibitor than KRAS inhibitor monotherapy.

Translocations occurred in 11 (61.1%) PCL patients; IGH::CCND1 and IGH::MYC were more frequent in PCL compared to MM (22% vs. 14%, p = NS, and 11% vs. 1%, p < 0.05). Druggable aberrations in BRAF, CCND1, PIK3R1, and RAS may be targeted in biomarker-driven therapeutic clinical trials.

Autologous PBL, gene engineered to express the PIK3CAE545K-specific TCR, suppressed the in vitro growth of two cancer cell lines, which endogenously expressed the PIK3CAE545K neoantigen. This study identified three PIK3CA-specific TCRs against two shared mutations, restricted by common HLA-class II molecules, using antigen-experienced TIL and memory PBL from patients with epithelial cancers and may further allow the development of off-the-shelf T cell immunotherapy strategies targeting PIK3CA.

Sotorasib is a targeted therapy approved for the treatment of KRAS G12C-mutated non-small cell lung cancer and is known to induce cytochrome P450 3A4 and potentially modulate P-glycoprotein activity. Because calcineurin inhibitors and mechanistic target of rapamycin inhibitors have narrow therapeutic windows, even modest reductions in exposure may predispose to acute rejection. Transplant clinicians should closely monitor drug levels and coordinate care with oncology teams when initiating sotorasib to maintain adequate immunosuppression and protect graft function.

P2, N=40, Recruiting, Mayo Clinic | Trial completion date: May 2027 --> Jul 2029 | Trial primary completion date: May 2026 --> Jul 2029

P1, N=171, Recruiting, Boehringer Ingelheim | N=94 --> 171 | Trial primary completion date: Jun 2028 --> Feb 2029

Our findings highlight the functional heterogeneity of myCAFs and identify TAGLN-expressing myCAFs as critical mediators of tumour progression, providing evidence that targeting stromal TAGLN may represent a promising therapeutic strategy for PDAC.

MEK inhibitors, especially trametinib and avutometinib in combination with defactinib, have recently demonstrated improved outcomes in recurrent disease, while new combination strategies are under active evaluation to overcome resistance mechanisms. Immunotherapy remains of limited efficacy, though biomarker-driven combinations are explored. Ongoing biomarker-guided trials are expected to refine treatment paradigms.

Impaired ER-phagy triggers protein aggregation, inflammation, and acinar-to-ductal metaplasia, promoting tumorigenesis. These findings highlight selective autophagy's role in cancer, with possible therapeutic implications.

P1, N=30, Recruiting, Henan Cancer Hospital | Not yet recruiting --> Recruiting