Abstract
A growing field of evidence suggests the involvement of oncogenic receptor tyrosine kinases (RTKs) in the transformation of malignant cells. Constitutive and abnormal activation of RTKs may occur in tumors either through hyperactivation of mutated RTKs or via functional upregulation by RTK-coding gene amplification. In several types of cancer prognosis and therapeutic responses were found to be associated with deregulated activation of one or more RTKs. Therefore, targeting various RTKs remains a significant challenge in the treatment of patients with diverse malignancies. However, a frequent issue with the use of RTK inhibitors is drug resistance. Autophagy activation during treatment with RTK inhibitors has been commonly observed as an obstacle to more efficacious therapy and has been associated with the limited efficacy of RTK inhibitors. In the present review, we discuss autophagy activation after the administration of RTK inhibitors and summarize the achievements of combination RTK/autophagy inhibitor therapy in overcoming the reported resistance to RTK inhibitors in a growing number of cancers.
Highlights
Intersection between receptor tyrosine kinases and autophagy Receptor tyrosine kinases (RTKs) are transmembrane glycoproteins that participate in the transduction of external signals into cells [1]
The present review aims to discuss autophagy activation as a possible mechanism involved in impeding the cytotoxicity of RTK inhibitors
The chief problem with the use of RTK inhibitors in clinical oncology is their targeting of multiple RTKs, which can evoke several side effects [66]
Summary
Intersection between receptor tyrosine kinases and autophagy Receptor tyrosine kinases (RTKs) are transmembrane glycoproteins that participate in the transduction of external signals into cells [1]. The most recent RTK-targeted therapy failed to improve the cure rate because the malignant cells activate defense mechanisms and acquire resistance [9]. Knowing that autophagy can impact sensitivity of cancer cells to RTK inhibitors, it can be expected that miRNAs are somehow involved in this regulation as well.
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