The research team led by Prof. Francesco Bertoni has published the results of a project in collaboration with the Group of Prof. Wymann at the University of Basel and the Colleagues at PIQUR Therapeutics in the journal Cancers.
mTOR is an atypical serine/threonine kinase often aberrantly activated in cancer cells because it is central in the regulation of cellular growth and metabolism. It is present in two complexes, mTOR complex 1 (TORC1) and mTOR complex 2 (TORC2), which differ for the presence of additional proteins. The first generation of mTOR inhibitors, such as sirolimus (rapamycin), temsirolimus, everolimus and ridaforolimus, inhibit only TORC1.
Chiara Tarantelli and Colleagues have studied the anti-tumor activity of the brain penetrant dual TORC1/2 inhibitor PQR620. PQR620 as single agent has an anti-tumor activity in lymphomas but this effect is largely cytostatic. However, the combination with the BCL2 inhibitor venetoclax led to cytotoxicity, which was also confirmed in xenograft models. The data support further evaluation of PQR620 as a single agent or in combination with venetoclax.
Tarantelli C, Gaudio E, Hillmann P, Spriano F, Sartori G, Aresu L, Cascione L, Rageot D, Kwee I, Beaufils F, Zucca E, Stathis A, Wymann MP, Cmiljanovic V, Fabbro D, Bertoni F.
The novel TORC1/2 kinase inhibitor PQR620 has anti-tumor activity in lymphomas as single agent and in combination of venetoclax.
Cancers (Basel) 2019, 11(6), 775; https://doi.org/10.3390/cancers11060775 (registering DOI)