TITLE:
Dual Epidermal Growth Factor Inhibition and Multi Targeted Epigenetic Therapy (MTET)
AUTHORS:
Mohammad Nezami, Steve Hager
KEYWORDS:
Epidermal Growth Factor, Lung Cancer, Epigenetic Therapies, Targeted Therapies, Afatinib
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.9 No.11,
November
14,
2018
ABSTRACT: Since
the discovery of tyrosine kinase inhibitors in treatment of lung cancer
harboring such actionable targets, many lives have been prolonged. To the same
extent, same group of patients have failed to benefit from this category of
drugs, in long run, either initially or during the course of treatments, simply
due to either known or unknown mechanism of resistance which occurs very often
in the first few months after initiation of therapy. The resistance is 100
percent expected, and no patient is
reported to be a waiver of such pattern. With best practices of oncology,
the average duration of response is expected to be below 12 months [1]. About half of the resistance is caused by
mutation at T790M in EGFR target, which can be revealed by liquid biopsy [1] [2]. The
most recent studies have revealed the significant role of epigenome in
controlling this complicated resistance pattern. We have learned that Histone
deacetylation, as opposed to promoter methylation, may contribute to the
epigenetic silencing and to EGFR TKI resistance in NSCLC [3] [4]. Here
we present a case study with a model of combinational therapy that targets the
EGFR molecule, (by small molecule inhibitor, Afatanib) with simultaneous
epigenetic modification of the target, (by application of multitargeted
epigenetic therapy (MTET) with significantly improved clinical results. We
propose further trials are needed to support such hypothesis, which if proved,
could significantly shift the current practices in management of this set of
cases in lung adenocarcinomas.