Title:Targeting Tumor Suppressor Networks for Cancer Therapeutics
Volume: 15
Issue: 1
Author(s): Xuning Emily Guo, Bryan Ngo, Aram Sandaldjian Modrek and Wen-Hwa Lee
Affiliation:
Keywords:
RB, p53, BRCA1, BRCA2, gene therapy, small molecule inhibitors, tumor suppressors.
Abstract: Cancer is a consequence of mutations in genes that control cell proliferation, differentiation and cellular homeostasis.
These genes are classified into two categories: oncogenes and tumor suppressor genes. Together, overexpression
of oncogenes and loss of tumor suppressors are the dominant driving forces for tumorigenesis. Hence, targeting oncogenes
and tumor suppressors hold tremendous therapeutic potential for cancer treatment. In the last decade, the predominant
cancer drug discovery strategy has relied on a traditional reductionist approach of dissecting molecular signaling
pathways and designing inhibitors for the selected oncogenic targets. Remarkable therapies have been developed using
this approach; however, targeting oncogenes is only part of the picture. Our understanding of the importance of tumor
suppressors in preventing tumorigenesis has also advanced significantly and provides a new therapeutic window of opportunity.
Given that tumor suppressors are frequently mutated, deleted, or silenced with loss-of-function, restoring their
normal functions to treat cancer holds tremendous therapeutic potential. With the rapid expansion in our knowledge of
cancer over the last several decades, developing effective anticancer regimens against tumor suppressor pathways has
never been more promising. In this article, we will review the concept of tumor suppression, and outline the major therapeutic
strategies and challenges of targeting tumor suppressor networks for cancer therapeutics.