Cytotoxic activity of KRAS inhibitors in combination with chemotherapeutics

The clinical potency of mutated KRAS-specific inhibitors needs to be improved by suitable drug combinations. Inhibition of downstream signaling cascades increases toxicity and other combinations exploited comprise G12C-directed inhibitors with SOS1 inhibitors, glucose/glutamine metabolic modulators, classical chemotherapeutics, and others. The most suitable inhibitor combinations corroborated in preclinical development await clinical verification.