The role of RICTOR amplification in targeted therapy and drug resistance

Abstract

The emergence of tyrosine kinase inhibitors (TKIs) has changed the current treatment paradigm and achieved good results in recent decades. However, an increasing number of studies have indicated that the complex network of receptor tyrosine kinase (RTK) co-activation could influence the characteristic phenotypes of cancer and the tumor response to targeted treatments. One of strategies to blocking RTK co-activation is targeting the downstream factors of RTK, such as PI3K-AKT-mTOR pathway. RICTOR, a core component of mTORC2, acts as a key effector molecule of the PI3K-AKT pathway; its amplification is often associated with poor clinical outcomes and resistance to TKIs. Here, we discuss the biology of RICTOR in tumor and the prospects of targeting RICTOR as a complementary therapy to inhibit RTK co-activation.

Keywords: Drug resistance; RICTOR; TKIs; mTORC2.

Fig. 1

The mechanisms by which RICTOR participating in tumor growth, invasion and drug resistance

Fig. 2

Alteration frequency and clinical outcome of RICTOR amplification in different cancers (a Alteration frequency of RICTOR amplification in different cancers. b Kaplan-Meier plot on overall survival in SCLC patients with/without RICTOR amplification. c Kaplan-Meier plot on overall survival in colorectal cancer patients with/without RICTOR amplification. d Kaplan-Meier plot on overall survival in esophageal squamous cell carcinoma patients with/without RICTOR amplification