Abstract
Cancer is a genetic disease, and this concept is now widely exploited by both scientists and clinicians to develop new genotype-selective anticancer therapeutics. Although the quest of cancer genomics is in its dawn, recognition of the widespread applicability of genetic interactions with biological processes of tumorigenesis is propelling research throughout academic fields. Lung cancer is the most common cause of cancer death worldwide, with an estimated 1.6 million deaths each year. Despite the development of targeted therapies that inhibit oncogenic mutations of lung cancer cases, continued research into new therapeutic approaches is required for untreatable lung cancer patients, and the development of therapeutic modalities has proven elusive. The “synthetic lethal” approach holds the promise of delivering a therapeutic regimen that preferentially targets malignant cells while sparing normal cells. We highlight the potential challenges in synthetic lethal anticancer therapeutics that target untreatable genetic alterations in lung cancer. We also discuss both challenges and opportunities regarding the application of new synthetic lethal interactions in lung cancer.
Highlights
The concept of synthetic lethality was introduced almost 100 years ago, and it has recently been exploited in various efforts to develop new genotype-selective anticancer therapeutics [1]
We provide an overview of the recent progress made in a synthetic lethal approach to lung cancer, including the most promising strategies for future developments
In 1986, Renato Dulbecco mentioned that the cancer-related proteins affect interacting networks, is not a summation of the isolated effects complete sequence of the human genome would be an essential tool for systematically discovering of oncogene activation and tumor suppressor gene inactivation [28]
Summary
The concept of synthetic lethality was introduced almost 100 years ago, and it has recently been exploited in various efforts to develop new genotype-selective anticancer therapeutics [1]. The synthetic lethality concept has been expanded to include a number of other related genetic concepts, such as induced essentiality, collateral sensitivity and synthetic dosage lethality, which are Medicines 2019, 6, 38; doi:10.3390/medicines6010038 www.mdpi.com/journal/medicines occurrence would be 0.01%, which means that 10,000 samples are required for a single assay To solve this issue, the construction of experimental models and the development of highly specific technological innovation have been promoted. Two genes are defined as synthetically lethal is if gene mutations that are categorized as loss-of-function or gain-of-function, and synthetic lethality simultaneous of both genesa genetics-based cause cell death while sparing normal cells We provide an overview of the recent progress made in a synthetic lethal approach to lung cancer, including the most promising strategies for future developments
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