Here is a research abstract, published in Blood, testing the viability of one of the new kinase inhibitors:
Targeting TORC2 in multiple myeloma with a new mTOR kinase inhibitor
* Corresponding author; email: email@example.com
Although preclinical work with rapalogs suggests potential in treatment of multiple myeloma (MM), they have been less successful clinically. These drugs allostearically inhibit the mTOR kinase primarily curtailing activity of the TORC1 complex. To assess if mTOR within the TORC2 complex could be a better target in MM, we tested a new agent, pp242, which prevents activation of TORC2 as well as TORC1. Although comparable to rapamycin against phosphorylation of the TORC1 substrates, p70S6kinase and 4E-BP-1, pp242 could also inhibit phosphorylation of AKT on serine 473, a TORC2 substrate, while rapamycin was ineffective. and apoptosis in MM cells. In addition, pp242 was an effective agent against primary MM cells in vitro and growth of 8226 cells in mice. Knockdown of the TORC2 complex protein, rictor, was deleterious to MM cells further supporting TORC2 as the critical target for pp242. TORC2 activation was frequently identified in primary specimens by immunostaining for AKT phosphorylation on S473. Potential mechanisms of upregulated TORC2 activity in MM were stimulation with IL-6 or IGF-1, and PTEN or RAS alterations. Combining pp242 with bortezomib led to synergistic anti-MM effects. These results support TORC2 as a therapeutic target in MM. PP242 was also more effective than rapamycin in achieving cytoreduction
Analyzing this data is way above my pay grade! My take on these studies: Myeloma is a sensitive, almost “wimpy” cancer. It responds to many different types of treatment. Trouble is, it never goes away. Think about it: Dex alone can have a profound, short term affect in many myeloma patients. The trick will be finding combinations which have a lasting impact.
Feel good and keep smiling! Pat