On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma

Abstract

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Targeting KRAS in Non-Small Cell Lung Cancer

“…Patients with active brain metastases were ineligible Adagrasib can penetrate the brain and cerebrospinal fluid (preclinical data) and has demonstrated antitumor activity against brain metastases (clinical data). adaptive resistance tumors (13). Both drugs are pending of being tested in early phase trials.…”

“…The frequency of KRAS mutations varies according to patient ethnicity, being more frequent in Western vs Asian populations (26% vs 11%), and more common in current or former smokers compared to non-smokers (30% vs 10%) ( 10 , 11 ). It has also been observed that most KRAS mutations are clonal and appear early in carcinogenesis ( 12 , 13 ). KRAS mutations are usually mutually exclusive of other predictive oncogenic mutations such as EGFR or ALK, although KRAS mutations may arise as a mechanism of resistance to targeted therapies ( 11 , 13 ).…”

“…It has also been observed that most KRAS mutations are clonal and appear early in carcinogenesis ( 12 , 13 ). KRAS mutations are usually mutually exclusive of other predictive oncogenic mutations such as EGFR or ALK, although KRAS mutations may arise as a mechanism of resistance to targeted therapies ( 11 , 13 ).…”

“…There are differences in the patterns of metastasis depending on the KRAS mutation, with bone dissemination being more frequent in the KRAS G12C mutation, while the KRAS G12V mutation frequently presents with pericardial and pleural involvement ( 13 , 16 , 17 ).…”

Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design

“…The fact that gene mutations in either EGFR or KRAS have been found to be associated with a higher CTC count could confirm the hypothesis that CTCs represent a more dangerous (aggressive or metastatic) subpopulation of cancer cells. KRAS (a small GTPase and member of the RAS protein family) transmits signals from transmembrane receptors such as EGFR into cells [106]. It participates in many critical cellular processes, such as proliferation, differentiation and survival.…”