KRAS G13A

In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

These findings imply the genetic basis of KRAS with immunotherapeutic target molecules based on a real-time platform. This study also suggests the highly heterogeneous nature of cancer cells, which may facilitate the assessment of clonal dynamics across a single patient's disease.

The combination of avutometinib and everolimus overcomes the activation of the PI3K/AKT/mTOR pathway which is an adaptive resistance mechanism to MAPK pathway inhibition. We have shown that avutometinib and everolimus induce synergistic anti-tumor effects preclinically, and preliminary data suggest clinically meaningful ORR and PFS in patients with KRAS mt NSCLC including non-G12C variants.

RAS mutations could be useful in future target anti-EGFR therapy and molecular CRC screening strategy in Morocco.

A tolerable intermittent dosing schedule targeting both the MAPK and PI3K pathways has been established. The combination of VS-6766 with everolimus has shown activity in patients with a variety of KRAS mutation variants including responses in KRAS mt NSCLC.