Abstract
Simple SummaryAlthough great breakthroughs have been made in cancer treatment following the development of targeted therapy and immune therapy, resistance against anti-cancer drugs remains one of the most challenging conundrums. Considerable effort has been made to discover the underlying mechanisms through which malignant tumor cells acquire or develop resistance to anti-cancer treatment. The Hippo signaling pathway appears to play an important role in this process. This review focuses on how components in the human Hippo signaling pathway contribute to drug resistance in a variety of cancer types. This article also summarizes current pharmacological interventions that are able to target the Hippo signaling pathway and serve as potential anti-cancer therapeutics.Chemotherapy represents one of the most efficacious strategies to treat cancer patients, bringing advantageous changes at least temporarily even to those patients with incurable malignancies. However, most patients respond poorly after a certain number of cycles of treatment due to the development of drug resistance. Resistance to drugs administrated to cancer patients greatly limits the benefits that patients can achieve and continues to be a severe clinical difficulty. Among the mechanisms which have been uncovered to mediate anti-cancer drug resistance, the Hippo signaling pathway is gaining increasing attention due to the remarkable oncogenic activities of its components (for example, YAP and TAZ) and their druggable properties. This review will highlight current understanding of how the Hippo signaling pathway regulates anti-cancer drug resistance in tumor cells, and currently available pharmacological interventions targeting the Hippo pathway to eradicate malignant cells and potentially treat cancer patients.
Highlights
As a powerful weapon to kill aberrantly fast-growing tumor cells, chemotherapy represents one of the most efficacious treatment strategies for the majority of cancer patients, immensely prolonging progression-free survival and improving quality of life
Hippo signaling pathway in human cancer cells contributes to anti-cancer drug resistance and how these mechanisms might be exploited to clinically benefit cancer patients
Ras association domain family 1 isoform A (RASSF1A) is epigenetically silenced by promoter DNA methylation in more than 50% of all solid tumors, and loss of it correlates with the acquisition of paclitaxel resistance in ovarian cancer and breast cancer patients [54,90,91]
Summary
As a powerful weapon to kill aberrantly fast-growing tumor cells, chemotherapy represents one of the most efficacious treatment strategies for the majority of cancer patients, immensely prolonging progression-free survival and improving quality of life. Combinations of multiple therapeutic agents have become the paradigm for cancer therapy as initial solutions to the resistance against single-agent treatment, drug resistance continues to be a huge obstacle [1]. A variety of mechanisms through which tumor cells develop resistance against anti-cancer agents have been defined, the exact biological processes remain incompletely understood. Improved therapeutic outcome and survival can be achieved from deciphering the biological determinants of drug resistance in tumors, which will guide the design of novel strategies to defeat drug resistance. Hippo signaling pathway in human cancer cells contributes to anti-cancer drug resistance and how these mechanisms might be exploited to clinically benefit cancer patients.
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