The development of therapeutic agents targeting the PI3K/Akt/mTOR pathway has been gaining momentum. The rapalogs are the most established group. New drug classes are emerging including those with single targets, those affecting multiple isoforms, and those seeking to inhibit multiple nodes within the signalling cascade. Data from clinical trials is contributing to the knowledge base of these novel compounds and is also posing further questions and challenges. Anti-cancer activity is being described but the overall response rates are lower than anticipated fuelling the need to better select patients and enrich target populations. Biomarkers are being utilized to achieve these aims and also to ensure desired pathway inhibition is occurring. Toxicities have been manageable and reversible in most cases. The next wave of studies is exploring PI3K/Akt/mTOR inhibitors administered in combination with hormones, cytotoxics, or other targeted therapies, amongst others. This chapter reviews the different classes of drugs in development as well as the pertinent findings from these clinical trials.
|Title of host publication||mTOR Inhibition for Cancer Therapy|
|Subtitle of host publication||Past, Present and Future|
|Editors||Monica Mita, Alain Mita, Eric K. Rowinsky|
|Place of Publication||Paris France|
|Pages||251 - 27|
|Number of pages||25|
|Publication status||Published - 2016|