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Nano-biosensors: A Custom-built Diagnosis
Published in Paula V. Messina, Luciano A. Benedini, Damián Placente, Tomorrow’s Healthcare by Nano-sized Approaches, 2020
Paula V. Messina, Luciano A. Benedini, Damián Placente
Despite their diagnostic and therapeutic potential, the clinical use of exosomes as cancer biomarkers is, however, still very limited. For example, a great proportion of non-small cell lung cancer (NSCLC) patients (≈60%) developed resistance to targeted epidermal growth factor receptor (EGFR) inhibitor therapy because of EGFR T790M mutation. Patients exhibiting EGFR T790M mutation were treated with third-generation tyrosine kinase inhibitors with a favourable projection; however, obtaining a tissue biopsy to confirm the mutation poses risks and is often not feasible. Castellanos-Rizaldos and co-workers (Castellanos-Rizaldos et al. 2018) developed and validated a novel test (exoNA) that overcomes the limited abundance of the mutation by simultaneously capturing and cross-examining exosomal RNA/DNA and cfDNA in a single step followed by a sensitive allele specific qPCR. The authors reported a 92% sensitivity and 89% of specificity in the detection of the T790M mutation using exoNA compared to tumour biopsy; 88% of sensitivity in patients with intrathoracic disease (M0/M1a) was also attained.
L858R EGFR mutant expressions in triple negative, luminaland HER2 breast cancer
Published in Cut Adeya Adella, Stem Cell Oncology, 2018
D. Budhiarko, T.P. Putra, A.T. Harsono, N. Masykura, G. Widjajahakim, A.R.H. Utomo, D. Tjindarbumi
EGFR mutation L858R is an important predictive genetic marker of sensitivity to TKIs, such as gefitinib, erlotinib, and afatinib in lung cancer. The prevalence of TKI sensitive EGFR mutation tends to be higher in Asian (30-55%) than Caucasian lung cancer patients (5-15%). In contrast to lung cancer, several EGFR TKI clinical trials in breast cancer have shown minimal efficacy or disappointing result [15-17]. The relatively rare frequency of TKI sensitising mutations in breast cancer (Y.H.-F. Teng et al., 2011; N. Ly et al., 2011) may explain poor response to TKI in trials that enrolled largely Caucasian and unselected breast cancer. Interestingly, few Caucasian patients had been shown to harbour T790M EGFR mutation that is known to confer TKI resistance (Bemanian et al., 2015).
Small-Molecule Inhibitors Targeting Receptor Tyrosine Kinases in Cancer
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Mohammad Hojjat-Farsangi, Gholamreza Khamisipour
Dacomitinib has been shown to be effective against NCI-H1975 cell line harboring EGFR L858R and T790M mutation in vitro and in vivo. These preclinical models recommend that this SMI might be highly effective against lung cancer cells that show resistant to erlotinib or gefitinib through T790M mutation in EGFR (Gonzales et al., 2008).
Mutation patterns of epidermal growth factor receptor gene in non-small cell lung cancer among Egyptian patients
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Wafaa H. Elmetnawy, Mona Qenawi, Salwa Sabet, Heba Bassiony
The T790M mutation at exon 20 is known as a point mutation at codon 790 substituting threonine with methionine in the EGFR gene, it was considered as a rare EGFR mutation [49]. This mutation represents 8.2% in our mutated cases, harmonizing with previous findings, which reported T790M occurrence in 1%–17% of all EGFR mutations, depending on the particular populations, and its presence encourages resistance acquirement and disease progression [50–54].
MOLECULAR DOCKING INVESTIGATION AND PHARMACOKINETIC PROPERTIES PREDICTION OF SOME ANILINOPYRIMIDINES ANALOGUES AS EGFR T790M TYROSINE KINASE INHIBITORS
Published in Egyptian Journal of Basic and Applied Sciences, 2021
Muhammad Tukur Ibrahim, Adamu Uzairu, Gideon Adamu Shallangwa, Sani Uba
As such, many second-generation EGFR tyrosine kinase inhibitors were developed to manage the resistance caused by the T790M mutation such as afatinib and docatininb. However, these inhibitors cannot achieve advantages over the first-generation reversible inhibitors due to the serious side effects, such as skin rash, diarrhea. It is thought that the activities against wild-type (WT) EGFR will limit the achievable activities against the T790M mutation in patients [15].