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A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
Published on: May 27, 2021
Cutting down the time to identify challenging tumor therapeutic targets and drug combinations using synthetic lethal
1Departments of Pharmacology and Chemistry, Fiske Drug Discovery Laboratory, University of Virginia, Box 800735, Charlottesville, VA, 22908-0735, USA.
Abstract:
Cancer drug discoverers and developers are blessed and cursed with a plethora of drug targets in the tumor cells themselves and the surrounding stromal elements. This bounty of targets has, at least in part, inspired the rapid increase in the number of clinically available small-molecule, biological, and cellular therapies for solid and hematological malignancies. Among the most challenging questions in cancer therapeutics, especially for small molecules, is how to approach loss-of-function gene mutations or deletions that encode tumor suppressors. A second mounting question is what are the optimal drug combinations. This article will briefly review the recent advances in exploiting in vitro and in vivo synthetic lethal screens to expose cancer pharmacological targets with the goal of developing new drug combinations.
Insights
Discovering new cancer drug combinations is crucial for treating solid and hematological malignancies. This review explores synthetic lethal screens to identify novel targets for effective cancer therapeutics.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Cancer drug discovery faces numerous targets within tumor cells and the tumor microenvironment.
- The development of small-molecule, biological, and cellular therapies has increased significantly for various cancers.
- Addressing loss-of-function mutations in tumor suppressor genes and determining optimal drug combinations remain key challenges in cancer therapeutics.
Purpose of the Study:
- To review recent advancements in synthetic lethal screens for identifying cancer drug targets.
- To highlight the potential of these screens in developing novel combination therapies for cancer.
Main Methods:
- Utilizing *in vitro* synthetic lethal screens.
- Employing *in vivo* synthetic lethal screens.
Main Results:
- Synthetic lethal screens have exposed numerous potential pharmacological targets in cancer.
- These screens provide a foundation for rational drug combination strategies.
Conclusions:
- Exploiting synthetic lethality through screening is a promising approach for cancer drug discovery.
- This strategy can lead to the development of more effective combination therapies to overcome therapeutic challenges, particularly for tumors with specific genetic alterations.
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