Abstract
Preclinical evaluation of drug combinations is challenging. In this mini-review we discuss the concept of synthetic lethality and how this can impact on the evaluation of drug combinations and its clinical development. We will also review novel combinations with immunologic agents and the concept of collateral lethality. We suggest that identification of synthetic lethality interactions including collateral lethality using novel drug combinations can speed up the drug development process. This approach may identify synergistic combinations in tumors with a specific molecular alteration, limiting toxicity to normal tissue. In addition, the combination of an immunotherapy with an agent targeting cancer cells have the potential for acting on different functions with no overlapping of toxicities. Here, we also discuss potential consequences of this approach in the design of early clinical studies.
Keywords: Synthetic lethality, drug combinations, therapeutic index, immunologic agents, immunotherapy, cancer.
Current Cancer Drug Targets
Title:Novel Synthetic Lethality Approaches for Drug Combinations and Early Drug Development
Volume: 17 Issue: 1
Author(s): Alberto Ocana and Atanasio Pandiella
Affiliation:
Keywords: Synthetic lethality, drug combinations, therapeutic index, immunologic agents, immunotherapy, cancer.
Abstract: Preclinical evaluation of drug combinations is challenging. In this mini-review we discuss the concept of synthetic lethality and how this can impact on the evaluation of drug combinations and its clinical development. We will also review novel combinations with immunologic agents and the concept of collateral lethality. We suggest that identification of synthetic lethality interactions including collateral lethality using novel drug combinations can speed up the drug development process. This approach may identify synergistic combinations in tumors with a specific molecular alteration, limiting toxicity to normal tissue. In addition, the combination of an immunotherapy with an agent targeting cancer cells have the potential for acting on different functions with no overlapping of toxicities. Here, we also discuss potential consequences of this approach in the design of early clinical studies.
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Cite this article as:
Ocana Alberto and Pandiella Atanasio, Novel Synthetic Lethality Approaches for Drug Combinations and Early Drug Development, Current Cancer Drug Targets 2017; 17 (1) . https://dx.doi.org/10.2174/1568009616666151203224714
DOI https://dx.doi.org/10.2174/1568009616666151203224714 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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