(ChemotherapyAdvisor) – Investigators have characterized how pro-invasion messenger RNAs direct prostate cancer invasion and metastasis downstream of oncogenic mTOR signaling — and then developed a clinically relevant ATP site inhibitor of mTOR, INK128, “which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure,” they noted in Nature, published online February 22.
“Many human cancers show hyperactivation of this pathway,” said Davide Ruggero, PhD, of the Helen Diller Family Comprehensive Cancer Center and the Multiple Myeloma Translational Initiative at UCSF. “Until now, we have not known how hyperactive mTOR perturbs the synthesis of certain proteins leading to fatal cancer.”
This work using ribosome profiling helps pinpoint why, in the past, drugs that target mTOR, such as rapamycin, have failed in clinical trials: They may block mTOR, but not completely. Preclinical research with INK128 has found that a mouse model of human prostate cancer treated with the agent did not metastasize and also demonstrated a strong therapeutic effect on human prostate-cancer cells.
INK128, now in clinical trials for different types of cancers, including multiple myeloma, is being developed by Intellikine, Inc., La Jolla, CA.