Journal of Thoracic Oncology

Running head: TOXICOLOGY AND PATHOLOGY
GENETIC ABERRATION IN LUNG CANCER
Name of the Student
Name of the University
Author Note

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Running head: TOXICOLOGY AND PATHOLOGY
Introduction
According to recent statistical reports, lung cancer has occupied a major part of the
population. There are two major categories of lung cancer named as non-small cell lung
cancer (NSCLC) and small cell lung cancer (Soria et al. 2018). The main compositions of
lung cancer are adenocarcinoma for 65% and 30% for squamous cell carcinoma. According
to various research studies, squamous cell carcinomas have been found to arise from a higher
mutation rate, which is mostly found in smokers. There is also a major type of lung cancer
known as EGFR mutation-positive cancer. One of the drugs known as osimertinib had shown
a survival without any cancer progression. The main molecular targets associated with lung
cancer include EGFR, ROS1, ALK and programmed cell death. Emerging (RET, MET and
NTRK) and elusive (MYC, KRAS, and TP53) are also the molecular targets for lung cancer
treatment. ENU mutagenesis (N-ethyl-N- nitrosourea) mutagenesis has been performed as in
various screening processes to identify the mechanism of resistance occurring in first and
second-line treatment with osimertinib (Lindeman et al. 2018). Most of the screening tests
proved that T790M resistance and C797S resistance were the most prominent resistances
observed in cases of lung cancer. This article will discuss the genetic aberrations associated
with lung cancer which includes the targets of drug use for the treatment of lung cancer. This
paper will also discuss the techniques to detect the targets for drug action during a condition
of lung cancer. Some of the most significant detecting the targets for drug action are NGS
(Next Generation Sequencing), Sanger sequencing and Real-time PCR (Polymerase Chain
Reaction).
Discussion
This section will review the existing reviewed and published pieces of literature
which focuses on the genetic alterations responsible for lung cancer and talks about the drug

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Running head: TOXICOLOGY AND PATHOLOGY
targets during the chemotherapy of lung cancer. According to Uchibori et al. (2018), EGFR
mutation is one of the most important underlying causes of lung cancer among the human
community. The survival rate of patients associated with EGFR positive mutation has
improved dramatically due to the introduction of EGFR-TKIs (EGFR tyrosine kinase
inhibitors). The first-line treatment used for lung cancer is EGFR-TKI showed a lower
survival rate than osimertinib. A significant reduction of lung cancer progression can occur
provided the person stops smoking. However, when lung cancer originates from a genetic
background, it becomes harder to control the progression. The authors successfully showed
that EGFR-TKI resistance mechanisms based on the first and second-line osimertinib by the
screening of ENU mutagenesis. According to the authors, T854A and C797S mutation has
been observed to afatinib resistance. According to Friedlaender et al. (2019) cancer of lungs
causes a high rate of mortality among the human population. Adenocarcinomas and
squamous cell carcinomas are the first disorders for which immunotherapy was discovered.
Treatment of targetable driver mutations is secondary. There are two major categories of lung
cancer named non-small cell lung cancer (NSCLC) and small cell lung cancer. The main
compositions of lung cancer are adenocarcinoma for 65% and 30% for squamous cell
carcinoma. According to various research studies, squamous cell carcinomas have been found
to arise from a higher mutation rate, which is mostly found in smokers. There is also a major
type of lung cancer known as EGFR mutation-positive cancer. A higher rate of mutation has
been observed for smokers since they are affected by squamous cell carcinomas. Two of the
most important problems in the identification of driver mutations and finding clinically
relevant mutations associated with lung cancer. According to the cancer genome Atlas,
frequent gene alterations have been used to identify the target of drugs required to neutralize
the mutation. Next-generation sequencing (NGS) has been observed to find the appropriate
landscape for the action of the drug against lung cancer. NGS has been used to identify the

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Running head: TOXICOLOGY AND PATHOLOGY
genetic rearrangements, copy number alterations, translocations and oncogenic fusion events
responsible for lung cancer. NGS is also cost-effective than other single-gene tests required to
identify the central; gene alterations responsible for the occurrence of non-squamous lung
cancer (NSCLC). NGS has also been observed as a highly specific and sensitive procedure to
test the potential impact of lung cancer and its effect after the action of therapeutic agents.
The primary genetic aberrations observed during the ERBB mutations, SqCC, and other
targets have been observed to be promising. TP53 mutations have been observed to be the
primary cause of lung cancer by NGS. Later, it has been stated that TP53 plays a major role
during the tumorigenesis process of epithelial lung cells. Cellular resistance to therapy has
been increasingly associated with genetic aberrations associated with lung cancer. In another
paper written by Gallant and Lovly (2018), it is stated that the identification of lung cancer as
a genetic disease cannot be rule out completely. The cancer taxonomies have been pushed
forward to categorize lung cancer according to the previously stated criteria. This study
successfully identified various mutations in genes responsible for the occurrence of lung
cancer. These mutated points in the gene is responsible for the secretion of abnormal proteins
that are targeted by various drugs used to treat lung cancer. The main genes responsible for
the occurrence of lung cancer are EGFR, ALK, ROS1 MET, NTRK and RET which are
directly targeted by drugs to reduce the progression of lung cancer. EGFR was identified as a
membrane-bound RTK (Receptor Tyrosine Kinase) which was used to search for epidermal
growth factor associated cognate receptor. EGFR was later recognized as the oncogene
inexorably linked with lung cancer. The emerging targets for lung cancer treatment include
(RET fusions, NTRK1/3 fusions, MET mutations, MET fusions, FGFR fusions, EGFR
fusions, HER2 mutations, AKT mutations, and RICTOR amp). Thus EGFR mutations have
been observed to be categorized under the group of emerging drug targets associated with the
treatment of lung cancer. The established targets for lung cancer include ALK fusions, ROS1