KRAS G13

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Feb 2027

P1, N=750, Active, not recruiting, Eli Lilly and Company | Recruiting --> Active, not recruiting

Across a CRC panel that included SNU-C5/WT and its 5-fluorouracil- and oxaliplatin-resistant derivatives, HT-29 (KRAS-wild-type), and HCT-8 and LoVo (KRAS-mutant), co-immunoprecipitation showed that PrPC forms complexes with the 37/67 kDa laminin receptor (RPSA), with PrPC-RPSA association particularly increased in KRAS-mutant HCT-8 and LoVo cells. Taken together, these findings suggest that extracellular PrPC supports RAS-AKT signaling, proliferation, and tumor-associated angiogenesis in KRAS-mutant colorectal cancer, and that PrPC neutralization additively enhances 5-fluorouracil activity in KRAS-mutant models. The data provide a preclinical basis for evaluating PrPC antibodies in combination with fluoropyrimidine-based regimens in patients with KRAS-mutant CRC.

In this phase I study, we test a pooled synthetic long peptide vaccine targeting the six KRAS mutations (G12V, G12A, G12R, G12C, G12D, G13D) with ipilimumab and nivolumab in resected pancreatic adenocarcinoma. The vaccine also generates cross-reactive T cells that recognize more than one mutant KRAS antigen. These findings support the safety and diverse anti-tumor immunity of mutant KRAS vaccines (NCT04117087).

P=N/A, N=12, Not yet recruiting, Cancer Hospital of Chinese Academy of Medical Sciences; Cancer Hospital of Chinese Academy of Medical Sciences

P1, N=32, Not yet recruiting, Zhejiang Cancer Hospital; Shanghai Ruihongdi Pharmaceutical Co., LTD

The cancer was refractory to regimens extrapolated from rectal cancer management (capecitabine with oxaliplatin, and irinotecan). Pelvic recurrence and osseous metastases were clearly radiosensitive. Tumor molecular profile showed microsatellite stable cancer with KRAS p.G13D and TP53 p.C176W mutations.

In conclusion, no significant associations between KRAS-G12 and overall survival were found for TAS-102 or TAS-Bev. Further research is needed to assess the impact of these mutations on combined TAS-Bev therapy prior to any clinical application.

We also include a systematic review of cutaneous HS cases, identifying only two cases with underlying hematologic transdifferentiation. The distinct clinical morphology, histopathologic characteristics, and immunohistochemical markers associated with each of these entities highlight a very rare and unique example of histiocytic transdifferentiation in the context of a hematologic malignancy.

Instead, some cases may reflect adult-onset RASopathies or early clonal proliferations with distinct biological behavior. Recognition of such cases warrants refinement of diagnostic criteria and may influence therapeutic decision-making.

Our results support a causal relationship between red meat and CRC and may inform tailored dietary and screening guidelines for CRC prevention.

Despite the historical challenges in targeting KRAS-mutant proteins, the findings of this study support the potential of natural products as scaffolds for anticancer drug discovery as a source for developing novel anticancer therapies. The identified phytochemicals from C. officinalis such as calendasaponin D and procyanidin A2 may serve as potential leads for future preclinical and experimental validation against KRAS-driven malignancies.