KRAS G12S

KRASmt and NRASmt are seen in 49% and 4% of mCRC, respectively. No clinically relevant differences were observed between different RASmt. KRASmt is a common subgroup for which the outcome hopefully can be improved with newly developed drugs.

The anticancer activities of SS-3091 and SS-30125 have been validated against the KRas G12D, G12C, G12V, and G12S mutants in various cancer cells. All findings underscore the potential of SS-3091 and SS-30125 as very promising active pan-KRas inhibitors.

This study introduced a preliminary integrative workflow for neoepitope identification. Findings indicate that the 21 candidate KRAS neoepitopes have the potential to be recognized by cytotoxic lymphocytes and trigger immune response. This positions them as promising elements  for anti-cancer vaccine formulations, pending successful in vitro, animal, and clinical studies.

The KRAS protein level correlated poorly with KRAS mRNA expression level and was not significantly associated with the type of mutation present. Interestingly, we found that patients with high KRAS protein level in their tumors had a better clinical outcome.

P1/2, N=72, Not yet recruiting, Sun Yat sen University Cancer Center; Sun Yat-sen University Cancer Center

Our findings provide evidence that splicing factor mutations can rescue splicing defects caused by oncogenic mutations. More broadly, they demonstrate a dynamic process of cascading selection where mutational events are positively selected in cancer genomes as a consequence of earlier mutations.

Using Kirsten rat sarcoma viral oncogene homolog (KRASG12S) and B-cell lymphoma 2 (Bcl-2) genes as targets, it is verified that the hairpin DNA oligonucleotides show cytotoxicity only to tumor cells but very low effects on normal cells. In addition, hairpin DNA oligonucleotides designed for KRAS inhibition, which are encapsulated in lipid nanoparticles, inhibit tumor growth in mice and demonstrate excellent antitumor efficacy in combination with gefitinib, but has little effect on normal tissues, suggesting that the proposed strategy enables highly selective tumor therapy and has the potential to give rise to a new class of nucleic acid drugs.

These results demonstrated that laparoscopic surgical approaches are effective and frequently the first surgical approach chosen for the treatment of ACUM, but that techniques to treat these conditions are not standardized. This case is the first to demonstrate mutations in ACUM, suggesting a potential role for cancer-associated somatic mutations in their genesis. Future developments in this area may include sending more of these samples for genetic analysis, improving our understanding of how these lesions are formed, while also working to standardize how they are removed.

Ras pathway inhibitors Trametinib and Rigosertib suppressed the lethality but not the reduced size phenotypes. In contrast, the lack of effects on the reduced size phenotypes would be consistent with small stature resulting from Raf- and PI3K-independent processes. We propose that this model can be useful for future mechanistic analysis and pharmacological screening and evaluation.

On March 25, 2024, the patient underwent the 3rd cycle of anti-tumor therapy "Tirellizumab 200 mg+albumin paclitaxel 400 mg+carboplatin 450 mg", and on April 9, 2024, Stevens-Johnson syndrome and toxic epidermolysis occurred, and the epidermolysis area reached more than 95%. After permanent discontinuation of immunosuppressants, anti-infection, hormone, nutritional support, immunoglobulin and other comprehensive treatment, the patient was eventually cured and successfully discharged.

Treatment with C14-PEI micelleplexes containing Cas9 mRNA and sgRNA targeting the KRAS G12S mutation significantly impairs the migration capability of A549 cells and increases apoptosis rates. These findings suggest that C14-PEI effectively disrupts KRAS signalling pathways, leading to reduced tumor cell proliferation and enhanced cell death.

P1/2, N=158, Active, not recruiting, Elicio Therapeutics | Recruiting --> Active, not recruiting