PI3K–AKT–mTOR and MYC

RTKs and RAS also activate PI3K, which converts the membrane lipid PIP2 into PIP3. PIP3 recruits and activates AKT, a kinase that blocks apoptosis, boosts glucose uptake and activates mTORC1 — the master regulator of protein synthesis and cell growth.

The tumor suppressor PTEN reverses PI3K by turning PIP3 back into PIP2. PIK3CA (PI3K) activating mutations and PTEN losses are among the most common events in breast, endometrial, prostate and brain cancers.

MYC is a transcription factor that, with its partner MAX, boosts expression of thousands of genes involved in ribosome production, metabolism and cell-cycle entry. Normally MYC is short-lived and tightly controlled.

Overactive MYC — through amplification or translocation — drives cells to grow and divide relentlessly, but also triggers apoptosis as a safeguard. That's why MYC-driven cancers usually also need an anti-apoptotic hit such as BCL-2 overexpression.