The Dual Role of Autophagy in Crizotinib-Treated ALK⁺ ALCL: From the Lymphoma Cells Drug Resistance to Their Demise

Abstract

Autophagy has been described as harboring a dual role in cancer development and therapy. Depending on the context, it can exert either pro-survival or pro-death functions. Here, we review what is known about autophagy in crizotinib-treated ALK+ ALCL. We first present our main findings on the role and regulation of autophagy in these cells. Then, we provide literature-driven hypotheses that could explain mechanistically the pro-survival properties of autophagy in crizotinib-treated bulk and stem-like ALK+ ALCL cells. Finally, we discuss how the potentiation of autophagy, which occurs with combined therapies (ALK and BCL2 or ALK and RAF1 co-inhibition), could convert it from a survival mechanism to a pro-death process.

Keywords

• anaplastic lymphoma kinase (ALK)
• anaplastic large cell lymphoma (ALCL)
• stem-like cells
• autophagy
• crizotinib
• targeted therapy