TY - JOUR
T1 - Targeting the apoptosis pathway in hematologic malignancies
AU - Zaman, Shadia
AU - Wang, Rui
AU - Gandhi, Varsha
N1 - Funding Information:
This work was supported in part by grants CLL PO1 CA81534 from the National Cancer Institute, Department of Health and Human Services and a Global Research Foundation European Alliance award.
PY - 2014/9
Y1 - 2014/9
N2 - Apoptosis is a cell death program that is well-orchestrated for normal tissue homeostasis and for removal of damaged, old or infected cells. It is regulated by intrinsic and extrinsic pathways. The intrinsic pathway responds to signals such as ultraviolet radiation or DNA damage and activates "executioner" caspases through a mitochondria-dependent pathway. The extrinsic pathway is activated by death signals induced, for example, by an infection that activates the immune system or receptor-mediated pathways. The extrinsic pathway signals also cascade down to executioner caspases that cleave target proteins and lead to cell death. Strict control of cellular apoptosis is important for the hematopoietic system as it has a high turnover rate. However, the apoptosis program is often deregulated in hematologic malignancies leading to the accumulation of malignant cells. Therefore, apoptosis pathways have been identified for the development of anticancer therapeutics. We review here the proteins that have been targeted for anticancer drug development in hematologic malignancies. These include BCL-2 family proteins, death ligands and receptors, inhibitor of apoptosis family proteins and caspases. Except for caspase activators, drugs that target each of these classes of proteins have advanced into clinical trials.
AB - Apoptosis is a cell death program that is well-orchestrated for normal tissue homeostasis and for removal of damaged, old or infected cells. It is regulated by intrinsic and extrinsic pathways. The intrinsic pathway responds to signals such as ultraviolet radiation or DNA damage and activates "executioner" caspases through a mitochondria-dependent pathway. The extrinsic pathway is activated by death signals induced, for example, by an infection that activates the immune system or receptor-mediated pathways. The extrinsic pathway signals also cascade down to executioner caspases that cleave target proteins and lead to cell death. Strict control of cellular apoptosis is important for the hematopoietic system as it has a high turnover rate. However, the apoptosis program is often deregulated in hematologic malignancies leading to the accumulation of malignant cells. Therefore, apoptosis pathways have been identified for the development of anticancer therapeutics. We review here the proteins that have been targeted for anticancer drug development in hematologic malignancies. These include BCL-2 family proteins, death ligands and receptors, inhibitor of apoptosis family proteins and caspases. Except for caspase activators, drugs that target each of these classes of proteins have advanced into clinical trials.
KW - Apoptosis
KW - Cancer therapeutics
KW - Hematologic malignancies
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U2 - 10.3109/10428194.2013.855307
DO - 10.3109/10428194.2013.855307
M3 - Review article
C2 - 24295132
AN - SCOPUS:84905016082
SN - 1042-8194
VL - 55
SP - 1980
EP - 1992
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 9
ER -