2017 Lasker Award to Prof. Mike Hall, the Father of "TOR" (Target of Rapamycin)

Rapamycin is among antibiotics isolated by a Canadian team from a soil bacterium in Rapa, Nui, Easter Island, in 1975.  Originally, its was recognized as an anti-fungal compound. However, later it was found to be a potent "immune suppressor" useful for organ transplantation. Interestingly, it has an anti-cancer activity as well. However, because of its immuno-suppressive activity, it has never been a favorable anti-cancer drug. To a big surprise, however, around 2009, Rapamycin was found by a US team led by Dr. David Harrison to extend significantly (by 9-14%) the lifespan of old (20 months) mice. Thus, it is among natural elixirs (longevity-promoters).

 In 1991, a Swiss team led by Prof. Mike Hall at University of Basel (Biozentrum), identified its direct target, a kinase,  in yeast. Since then, this kinase is called "target of rapamycin" (TOR), and a mammalian homolog of TOR is called mTOR. In other words, mTOR is an oncogenic/ ageing kinase, as is PAK1. Is TOR essential for melanogenesis as well, as is PAK1?  According to 2016 article by a Taiwanese group, Hinokitiol (heptagonal ring compound) inhibits melano-genensis of B16F10 melanoma cells by inactivating mTOR.  Thus, it is most likely that mTOR is a melanogenic kinase. The PAK1-blockers called ivermectin causes autophagy through PAK1-mTOR pathway, clearly indicating that mTOR is down-stream of PAK1.

However, according to 2012 article by a Korean group, rapamycin promotes melanogenesis, instead of suppressing it.  Thus, there must be another target of rapamycin (called TOR2) in mammals, in addition to mTOR. Furthermore, KO (knock-out) of PAK1 promotes immune system, suggesting that PAK1 is immuno-suppressive, just like rapamycin.  Thus, immuno-suppressive effect of rapamycin must be due to a third target called TOR3, which is not down-stream of PAK1. Therefore, for cancer therapy it would be desirable to develop a new rapamycin derivative which does not interact with TOR3. 

Nevertheless, Prof. Mike Hall became a 2017 Lasker awardee.  Thus, it is most likely that PAK1 pioneer(s) would also join the "Lasker Club" or "Nobel Club" in a not-distant future.