Cancer Metabolism and the Evasion of Apoptotic Cell Death.

Cellular growth and proliferation depend upon the acquisition and synthesis of specific metabolites. These metabolites fuel the bioenergy, biosynthesis, and redox potential required for duplication of cellular biomass. Multicellular organisms maintain tissue homeostasis by balancing signals promoting proliferation and removal of cells via apoptosis. While apoptosis is in itself an energy dependent process activated by intrinsic and extrinsic signals, whether specific nutrient acquisition (elevated or suppressed) and their metabolism regulates apoptosis is less well investigated. Normal cellular metabolism is regulated by lineage specific intrinsic features and microenvironment driven extrinsic features. In the context of cancer, genetic abnormalities, unconventional microenvironments and/or therapy engage constitutive pro-survival signaling to re-program and rewire metabolism to maintain survival, growth, and proliferation. It thus becomes particularly relevant to understand whether altered nutrient acquisition and metabolism in cancer can also contribute to the evasion of apoptosis and consequently therapy resistance. Our review attempts to dissect a causal relationship between two cancer hallmarks, i.e., deregulated cellular energetics and the evasion of programmed cell death with primary focus on the intrinsic pathway of apoptosis.