Publication Date:
2015-10-08
Description:
Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. Driver mutations that cause loss-of-function in tumor suppressor genes had been thought of as undruggable because of technical difficulties or mechanistic complexity. Recent advances in cancer genomics, drug design and development, and bioinformatic tools have revealed new therapeutic opportunities for targeting tumor suppressor mutations.
Print ISSN:
0265-9247
Electronic ISSN:
1521-1878
Topics:
Biology
,
Medicine
Permalink