Cancer Stories: The Art Of Oncology

Wall Street Doesn’t Believe in This Target

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Synopsis

"Wall Street doesn't believe in this target," by Dario Altieri. A scientist shares his 12-year journey that led to the discovery of a drug now in clinic.   TRANSCRIPT Narrator: Wall Street Doesn’t Believe in This Target by Dario C. Altieri, MD (10.1200/JCO.22.00180) March 2, 2009. Just published in the Journal of Clinical Investigation.1 And we even got the cover. Twists and turns of heat shock protein-90 (Hsp90), the chaperone, the evolutionary capacitor. Great name and important cancer target. People smiled when I talked about this at the Hsp90 conference. No, no, really there is a lot of it in mitochondria, and only in mitochondria of tumor cells. And, I don’t know why, but Hsp90 drugs don’t touch it: somehow, they don’t get to mitochondria. So, I made my own. Took an old Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin and attached it to triphenylphosphonium, a carrier that basically gets anything into the mitochondria. No, of course, I didn’t do the synthesis in my laboratory. What do I know about