Highlights in Resistance Mechanism Pathways for Combination Therapy

Abstract

Combination chemotherapy has been a mainstay in cancer treatment for the last 60 years. Although the mechanisms of action and signaling pathways affected by most treatments with single antineoplastic agents might be relatively well understood, most combinations remain poorly understood. This review presents the most common alterations of signaling pathways in response to cytotoxic and targeted anticancer drug treatments, with a discussion of how the knowledge of signaling pathways might support and orient the development of innovative strategies for anticancer combination therapy. The ultimate goal is to highlight possible strategies of chemotherapy combinations based on the signaling pathways associated with the resistance mechanisms against anticancer drugs to maximize the selective induction of cancer cell death. We consider this review an extensive compilation of updated known information on chemotherapy resistance mechanisms to promote new combination therapies to be to discussed and tested.

Hippo/YAP Signaling Pathway: A Promising Therapeutic Target in Bone Paediatric Cancers?

“…Schematically, two types of resistance mechanisms to chemotherapy can be described: Innate resistance that is intrinsic to the cell and acquired resistance that appears after treatment. Different mechanisms may be involved in cells-resistance acquisition, such as ABC transporters, amplification of therapeutic targets, appearance of mutations on therapeutic targets, or activation of alternative survival signaling pathways [120][121][122]. Understanding and deciphering the molecular mechanisms underlying this cells-resistance process is essential for adapting treatments and preventing relapse.…”

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

“…Drugs targeting the pathways related to cancer development can improve the prognosis if used in the early treatment of some cancers. However, these targeted treatments can cause drug resistance in tumor cells resulting in the failure of therapies [6][7][8][9]. Tumor resistance can be divided into two categories, i.e., inherent and acquired.…”

Cannabinoid Combination Induces Cytoplasmic Vacuolation in MCF-7 Breast Cancer Cells

“…Several studies have evaluated the use of drug combinations to overcome these chemotherapy-associated problems. Some advantages, including a reduction in the required dose [ 22 , 23 ], minimal potential to induce toxicity in the host, a reduction in the cost associated with therapy [ 23 ], and the minimal risk of developing drug resistance [ 24 , 25 ] have been associated with the various studies. Consequently, this study aimed to investigate the potential use of cannabinoid combinations to amplify therapeutic efficacy by simultaneously activating multiple anti-cancer mechanisms in breast cancer cell lines.…”