Clinical relevance of apoptotic regulatory proteins in colorectal cancers

Dysregulation of apoptosis or programmed cell death is a hallmark of human cancers that contributes to tumor development and progression, and may confer treatment resistance and therapeutic failure. Apoptosis is governed by both a mitochondria-mediated and a death receptor (DR)-mediated pathway. Within human cancer cells, both apoptotic pathways are regulated by proapoptotic and prosurvival Bcl-2 family proteins. Loss of proapoptotic genes or, alternatively, upregulation of prosurvival genes may lead to tumorigenesis in preclinical models. Expression of Bcl-2 family proteins has been shown to provide prognostic information in certain malignancies, including colon cancers, and therefore may be useful in determining which patients are more likely to suffer recurrence and metastasis. Such markers may assist in selecting patients to receive adjuvant chemotherapy and represent potential targets for therapeutic intervention. In the therapeutic arena, small molecule Bcl-2/Bcl-x _L antagonists and DR agonists have been developed that enhance chemosensitivity in preclinical models and currently are undergoing evaluation in cancer patients. This review focuses on the current status of apoptotic regulatory proteins as biomarkers in colorectal cancers and their potential clinical utility.