2021
DOI: 10.3390/cancers13246332
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Targeting KRAS in NSCLC: Old Failures and New Options for “Non-G12c” Patients

Abstract: Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene mutations are among the most common driver alterations in non-small cell lung cancer (NSCLC). Despite their high frequency, valid treatment options are still lacking, mainly due to an intrinsic complexity of both the protein structure and the downstream pathway. The increasing knowledge about different mutation subtypes and co-mutations has paved the way to several promising therapeutic strategies. Despite the best results so far having been obtained in pa… Show more

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Cited by 10 publications
(8 citation statements)
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“…KRAS mutations are dominant in lung, colorectal, and pancreatic cancers [49] with various types of mutations. G12V mutation [50], carried by Patient #1 in our study, represents around 22% of all KRAS mutations involving the replacement of glycine by valine. In the less common G12D mutation (16%) found [51] in Patient #3, a glycine is replaced by an aspartic acid mutation resulting from a G>A substitution.…”
Section: Discussionmentioning
confidence: 60%
“…KRAS mutations are dominant in lung, colorectal, and pancreatic cancers [49] with various types of mutations. G12V mutation [50], carried by Patient #1 in our study, represents around 22% of all KRAS mutations involving the replacement of glycine by valine. In the less common G12D mutation (16%) found [51] in Patient #3, a glycine is replaced by an aspartic acid mutation resulting from a G>A substitution.…”
Section: Discussionmentioning
confidence: 60%
“…KRAS -mutant NSCLC represents a genetically heterogeneous subgroup with a high frequency of co-occurring mutations in associated pathways, which should be considered when evaluating the treatment outcome [ 23 ]. At least at the time of diagnosis, KRAS mutations were described to be mutually exclusive with other alterations in NSCLC patients such as EGFR and BRAF mutations, as well as ALK and ROS rearrangements [ 24 ]. However, rare co-occurrence with EGFR (1.2%) and BRAF (1.2%) has been found, and co-occurring mutations with TP53 , PTEN , and STK11 have been described previously [ 21 , 23 , 25 , 26 ].…”
Section: Discussionmentioning
confidence: 99%
“…Clinical trials for NSCLC patients with KRAS non-G12C mutations have previously been reviewed [ 37 ]. The long-term efficacy of the current KRAS G12C inhibitors remains unclear, mostly due to toxicity and acquired resistance mechanisms [ 26 , 29 , 38 , 39 ].…”
Section: Strategies To Target Oncogenic Mutant Krasmentioning
confidence: 99%