Synthetic lethality on drug discovery: an update on cancer therapy

ABSTRACT

Introduction

A novel anticancer therapy is the need of the hour due to growing incidences of resistance to first line cancer chemotherapy. Synthetic lethality (SL) is one of the new age treatment methods being explored for combating the resistance to anticancer agents. In this method, cell mutations are exploited for the development of new therapeutic agents, where, if there is loss of function of one gene, the cell mutations can still be fixed by alternative machinery but if two genes involved in DNA repair undergo loss of function, it causes lethality to the cell.

Areas covered

The authors condense findings of SL-based novel anticancer regimen. The review emphasizes some of the SL based clinical and preclinical studies of novel targets and therapy.

Expert opinion

SL conceptualizes a resolution against treatment resistance to anticancer regimen by recognition of therapeutic vulnerabilities in particular cancer cells. A multitude of clinical trials associated with SL and DNA repair are being conducted that will be useful in obtaining a clearer picture pertaining to the use of cancer biomarkers and effectiveness of drugs acting via target-based molecular changes. Furthermore, new anticancer regimen focused on personalized medicines will emerge basing their development upon SL.

KEYWORDS:

• Synthetic lethality
• PARP
• BRCA
• cancer

Article Highlights

• Synthetic lethality is a potential solution to encounter tumor specific mutations to develop anticancer therapeutics.

• RNA interface and CRISPR-Cas9 are the major tools used for synthetic lethality screening.

• PARP inhibitors are the earliest approved drugs that take advantage of synthetic lethality.

• MYC family genes MYC, MYCN, and MYCL of transcription factors represent another interesting target of synthetic lethality interactions.

• Combined therapy of synthetic lethal agent and conventional chemotherapy can possibly alter the way cancer is treated.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.