title: Putting the pieces together: How is the mitochondrial pathway of apoptosis regulated in cancer and chemotherapy?
abstract: In order to solve a jigsaw puzzle, one must first have the complete picture to logically connect the pieces. However, in cancer biology, we are still gaining an understanding of all the signaling pathways that promote tumorigenesis and how these pathways can be pharmacologically manipulated by conventional and targeted therapies. Despite not having complete knowledge of the mechanisms that cause cancer, the signaling networks responsible for cancer are becoming clearer, and this information is serving as a solid foundation for the development of rationally designed therapies. One goal of chemotherapy is to induce cancer cell death through the mitochondrial pathway of apoptosis. Within this review, we present the pathways that govern the cellular decision to undergo apoptosis as three distinct, yet connected puzzle pieces: (1) How do oncogene and tumor suppressor pathways regulate apoptosis upstream of mitochondria? (2) How does the B-cell lymphoma 2 (BCL-2) family influence tumorigenesis and chemotherapeutic responses? (3) How is post-mitochondrial outer membrane permeabilization (MOMP) regulation of cell death relevant in cancer? When these pieces are united, it is possible to appreciate how cancer signaling directly impacts upon the fundamental cellular mechanisms of apoptosis and potentially reveals novel pharmacological targets within these pathways that may enhance chemotherapeutic success.
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, 1425 Madison Avenue, Box 1130, New York, NY 10029, USA.|Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.|The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.|The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.|The Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.
authors.forename: Rana
authors.initials: R
authors.lastname: Elkholi
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, 1425 Madison Avenue, Box 1130, New York, NY 10029, USA.|Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.|The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.|The Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.
authors.forename: Thibaud T
authors.initials: TT
authors.lastname: Renault
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, 1425 Madison Avenue, Box 1130, New York, NY 10029, USA.|Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.|The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.|The Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.
authors.forename: Madhavika N
authors.initials: MN
authors.lastname: Serasinghe
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, 1425 Madison Avenue, Box 1130, New York, NY 10029, USA.|Department of Dermatology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.|The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.|The Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.|The Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY 10029, USA.
authors.forename: Jerry E
authors.initials: JE
authors.lastname: Chipuk
keywords: Apoptosis; BCL-2 family; BH3 mimetics; Cancer; Mitochondria; Oncogenes; Signaling; Tumor suppressors