Dactolisib (codenamed NVP-BEZ235 and BEZ-235, also known as RTB101) is an imidazoquinoline derivative acting as a

PI3K inhibitor Phosphoinositide 3-kinase inhibitors (PI3K inhibitors) are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3 ...

. It also inhibits

mTOR The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. ...

. It is being investigated as a possible cancer treatment. It has been shown to be toxic to Waldenström's macroglobulinemia cells. It was the first PI3K inhibitor to enter clinical trials, in 2006. A phase IB/II clinical trial for locally advanced or metastatic HER2 negative breast cancer has completed. A phase II clinical trial for advanced

pancreatic neuroendocrine tumor Pancreatic neuroendocrine tumours (PanNETs, PETs, or PNETs), often referred to as "islet cell tumours", or "pancreatic endocrine tumours" are neuroendocrine neoplasms that arise from cells of the endocrine (hormonal) and nervous system within t ...

s (pNET) had initially reported results, but was later terminated because insufficient normal tissue tolerance to the drug. A phase I clinical trial of BEZ235 in patients with advanced renal cell carcinoma had to be terminated prematurely due to toxicity and a lack of clinical efficacy . Another Phase Ib study on patients with various solid cancers found severe normal tissue toxicity as well when BEZ235/Dactolisib was administered in combination with the mTOR inhibitor Everolimus. The authors concluded that the combination of both drugs demonstrated limited efficacy and tolerance. BEZ235 systemic exposure increased in a dose-proportional manner while oral bioavailability was quite low, which may be related to gastrointestinal-specific toxicity . A phase I study of BEZ-235 to treat acute lymphoid leukaemia was initiated in 2012, but no results were published since then. A phase 2a randomized, placebo-controlled clinical trial published in 2018 showed that

everolimus Everolimus, sold under the brand name Afinitor among others, is a medication used as an immunosuppressant to prevent rejection of organ transplants and as a targeted therapy in the treatment of renal cell cancer and other tumours. It is the 40 ...

in combination with dactolisib decreased the rate of reported infections in an elderly population.

References

Experimental cancer drugs Imidazoquinolines Phosphoinositide 3-kinase inhibitors Quinolines {{antineoplastic-drug-stub