The detection of actionable driver mutations in non-small cell lung cancer (NSCLC) has paved the road to “precision medicine”. Besides roughly 10% of patients with activating EGFR mutations, rare mutations like rearrangements of ALK, ROS1, RET, or NTRK have been proven to benefit from selective kinase inhibition. For these aberrations, the therapeutic armory is constantly increasing, accompanied by marked improvements in the prognosis. For nearly four decades since detection, mutated KRAS in lung cancer has been acting as an antithesis of modern therapy approaches: present in up to 30% of all NSCLC, molecularly tiny, equipped with a picomolar affinity to its only substrate - briefly: undruggable. Recently it could be demonstrated that the most common KRAS mutation in NSCLC, p.G12C, can be used for covalent cystine binding in the inactive state. The competitive “Game of Thrones'' opened the gates for KRAS-focused research with strong links to the clinics.
Within this Research Topic, we aim to provide an overview on the recent preclinical and clinical activities of targeting KRAS in NSCLC, including ongoing efforts to improve the outcome by targeting guanine nucleotide exchange factors (GEFs), by inhibiting the active (GTP-bond) state, by combining treatment with other targeted approaches or treatment modalities, and by focusing on the non-p.G12C subgroups.
This Research Topic will be focused on the progress and controversies in translational and clinical research on KRAS targeting in NSCLC. We welcome Original Research, Review articles, Perspective and Opinion articles, and unique Case Reports, which are aimed at deepening the translational/biological/genomics/clinical landscape of patients affected by KRAS mutated NSCLC, exploring epidemiology, diagnosis, prognosis, drug development, resistance mechanisms, as well as rationale for combination.
The detection of actionable driver mutations in non-small cell lung cancer (NSCLC) has paved the road to “precision medicine”. Besides roughly 10% of patients with activating EGFR mutations, rare mutations like rearrangements of ALK, ROS1, RET, or NTRK have been proven to benefit from selective kinase inhibition. For these aberrations, the therapeutic armory is constantly increasing, accompanied by marked improvements in the prognosis. For nearly four decades since detection, mutated KRAS in lung cancer has been acting as an antithesis of modern therapy approaches: present in up to 30% of all NSCLC, molecularly tiny, equipped with a picomolar affinity to its only substrate - briefly: undruggable. Recently it could be demonstrated that the most common KRAS mutation in NSCLC, p.G12C, can be used for covalent cystine binding in the inactive state. The competitive “Game of Thrones'' opened the gates for KRAS-focused research with strong links to the clinics.
Within this Research Topic, we aim to provide an overview on the recent preclinical and clinical activities of targeting KRAS in NSCLC, including ongoing efforts to improve the outcome by targeting guanine nucleotide exchange factors (GEFs), by inhibiting the active (GTP-bond) state, by combining treatment with other targeted approaches or treatment modalities, and by focusing on the non-p.G12C subgroups.
This Research Topic will be focused on the progress and controversies in translational and clinical research on KRAS targeting in NSCLC. We welcome Original Research, Review articles, Perspective and Opinion articles, and unique Case Reports, which are aimed at deepening the translational/biological/genomics/clinical landscape of patients affected by KRAS mutated NSCLC, exploring epidemiology, diagnosis, prognosis, drug development, resistance mechanisms, as well as rationale for combination.
