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Overview
Cancer cells are resistant to the stimuli that cause programmed cell death (apoptosis) in normal cells because they contain activated survival signaling pathways. This resistance to apoptosis allows cancer cells to grow under conditions of stress, low oxygen and inadequate nutrient supply found in tumors, whereas normal cells die in this environment. The abrogation of normal apoptotic pathways is a cause of resistance to many oncology drugs that kill cancer cells by inducing apoptosis. Consequently, survival signaling pathways, including the phosphotidylinositol-3 kinase (PI-3K)/AKT pathway, provide rational molecular targets for the development of new cancer drugs.
PI-3K is the nodal point of control of cellular responses including signaling of cell survival and growth, migration, metabolism and more. Deregulation of this critical pathway occurs through multiple mechanisms, including activating mutations of PI-3K or AKT, or loss of function mutations in PTEN, a protein that attenuates PI-3K activity. Due to its central role in regulating growth, proliferation and survival, the PI-3K pathway is found to be a key contributing factor to a number of human cancers, particularly ovarian, head and neck, urinary tract, cervical, prostate, endometrial and small cell lung cancers and gliomas.
PI-3 Kinase (PI-3K) Signaling
- PI-3K regulates diverse cancer-related pathways
- Signaling through PI-3K is deregulated in a variety of human tumors
- PX-866 potently inhibits alpha, delta and gamma isoforms of PI-3K, resulting in inhibition of downstream signaling proteins including p-AKT, p-mTOR, and p-S6
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