Circulating tumor DNA in advanced solid tumors: Clinical relevance and future directions
CA-A CANCER JOURNAL FOR CLINICIANS
Authors: Cheng, Michael L.; Pectasides, Eirini; Hanna, Glenn J.; Parsons, Heather A.; Choudhury, Atish D.; Oxnard, Geoffrey R.
Abstract
The application of genomic profiling assays using plasma circulating tumor DNA (ctDNA) is rapidly evolving in the management of patients with advanced solid tumors. Diverse plasma ctDNA technologies in both commercial and academic laboratories are in routine or emerging use. The increasing integration of such testing to inform treatment decision making by oncology clinicians has complexities and challenges but holds significant potential to substantially improve patient outcomes. In this review, the authors discuss the current role of plasma ctDNA assays in oncology care and provide an overview of ongoing research that may inform real-world clinical applications in the near future.
p38 alpha MAP kinase inhibitors to overcome EGFR tertiary C797S point mutation associated with osimertinib in non-small cell lung cancer (NSCLC): emergence of fourth-generation EGFR inhibitor
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Authors: Ahmad, Iqrar; Shaikh, Matin; Surana, Sanjay; Ghosh, Arabinda; Patel, Harun
Abstract
The third-generation EGFR (epidermal growth factor receptor) inhibitors selectively and irreversibly target EGFR-T790M and other activating EGFR mutations. Osimertinib is the only FDA-approved third-generation inhibitor, which has a good potency against the EGFR-T790M mutant with minimal toxicities and excellent selectivity for wild-type EGFR. EGFR tertiary Cys797 to Ser797 (C797S) point mutation emanate rapidly after the treatment of osimertinib, which is an undruggable mutation to all three existing generation drugs. Recently, trisubstituted imidazoles were reported based on an off-target hit of a p38 alpha MAPK (mitogen-activated protein kinase) inhibitor as the fourth-generation EGFR-TKIs to overcome the C797S resistance by inhibiting the clinically relevant triple mutant kinase L858R/T790M/C797 EGFR. Here, we are reporting the clinical trial p38 alpha MAPK kinase inhibitors SD-06, Amgen 16, RWJ67657 and SCIO-323 as L858R/T790M/C797S EGFR TK inhibitors to overcome the problem of drug resistance in non-small cell lung cancer (NSCLC). Communicated by Ramaswamy H. Sarma
COA
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