Par-4 as a potential target for cancer therapy.
BACKGROUND
Despite extensive research, cancer continues to be a leading cause of death worldwide and is expected to continue to rise as a result of an aging population. Therefore, new therapies are constantly being developed. Par-4 is a naturally occurring tumor suppressor protein that is capable of inducing apoptosis in cancer, but not normal cells. For this reason, Par-4 offers an attractive target for development of cancer therapy, particularly of difficult to treat cancers.


METHODS
The mechanisms by which Par-4 induces cell death are summarized. The ways that Par-4 is controlled in cancer cells are discussed. We discuss how different research groups have developed ways to overexpress and/or activate Par-4 in vitro and in vivo. The studies described demonstrate that when Par-4 levels and/or activity are increased, susceptibility to apoptosis is enhanced and tumor growth is inhibited.


CONCLUSIONS
Par-4 is a promising therapeutic protein that can be overexpressed and/or activated to induce apoptosis in a cancer-selective manner. This cancer selectivity is important given that the side-effects of chemotherapeutics can be as debilitating as cancer itself. However, there are key issues that need to be addressed to optimize the effects of Par-4 in patients.
Penn State Hershey Cancer Institute, 500 University Drive, Hershey, PA 17033, USA. rirby@hmc.psu.edu
Rosalyn B
RB
Irby
Christina L B
CL
Kline
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C101296:prostate apoptosis response-4 protein