PI3K/AKT Inhibitors as Sensitizing Agents for Cancer Chemotherapy

Resistance to chemotherapeutic drugs is a major obstacle for their successful clinical application. The PI3K/Akt pathway has become a key driver of resistance to diverse chemotherapies by promoting multidrug resistance (MDR), cancer stem cell survival, compensatory activation of downstream effectors, so on. Therefore, PI3K/Akt inhibitors are designed to circumvent resistance as sensitizing agents by combining with other antitumor drugs. Synergistic effects have been attained by some combinations in the preclinical and clinical contexts, while proper safety being kept in cancer patients. This chapter will describe mechanisms for the PI3K/Akt pathway involvement in various resistances to chemotherapies, followed by the applications of typical novel PI3K/Akt inhibitors as sensitizing agents.