Selective anticancer strategies via intervention of the death pathways relevant to cell transformation.
Apoptosis is an important physiological process that promotes tissue homeostasis by eliminating unnecessary or malfunctioning cells. Abnormality in this process contributes to tumorigenesis, as well as the resistance to cancer treatment by radiation and chemotherapy. Restoration of normal apoptosis would not only promote cancer cell death and halt tumor progression, but also increase the response to many current cancer therapies. Although apoptosis induction is an important principle of currently used radiation and chemotherapy treatment, uncovering the mechanisms that govern this process, and which are lost during transformation, represents an important direction for realizing improved therapies for the future. This article first briefly reviews aspects of current discovery strategies for new anticancer therapeutics based on intervening in cell death pathways, and then discusses in more detail several cancer-relevant death pathways, which are disabled during transformation and which can be targeted therapeutically. These include anoikis/cell adhesion; energy metabolism and the unfolded protein response. Finally, we introduce a new concept, which utilizes cancer-specific apoptosis induced by oncolytic viruses. The discussion of these topics involves novel targets, compounds and virotherapy.
Li
Q-X
QX
Drug Development, iTherX Pharmaceuticals Inc., San Diego, CA 92121, USA. li@itherx.com
Yu
D H
DH
Liu
G
G
Ke
N
N
McKelvy
J
J
Wong-Staal
F
F
D000818:Animals; D023102:Anoikis / Q000187:drug effects; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002448:Cell Adhesion; D015687:Cell Hypoxia; D002471:Cell Transformation, Neoplastic; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D017510:Protein Folding
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D005947:Glucose