Cancer chemotherapy resistance is one of the most critical obstacles in cancer therapy. One of the well-known mechanisms of chemotherapy resistance is the change in the mitochondrial death pathways which occur when cells are under stressful situations, such as chemotherapy. Mitophagy, or mitochondrial selective autophagy, is critical for cell quality control because it can efficiently break down, remove, and recycle defective or damaged mitochondria. As cancer cells use mitophagy to rapidly sweep away damaged mitochondria in order to mediate their own drug resistance, it influences the efficacy of tumor chemotherapy as well as the degree of drug resistance. Yet despite the importance of mitochondria and mitophagy in chemotherapy resistance, little is known about the precise mechanisms involved. As a consequence, identifying potential therapeutic targets by analyzing the signal pathways that govern mitophagy has become a vital research goal. In this paper, we review recent advances in mitochondrial research, mitophagy control mechanisms, and their implications for our understanding of chemotherapy resistance.

Recently, two tropomycin receptor kinase (Trk) inhibitors, larotrectinib and entrectinib, have been approved for Trk fusion-positive cancer patients. Clinical trials for larotrectinib and entrectinib were performed with patients selected based on the presence of Trk fusion, regardless of cancer type. This unique approach, called tissue-agnostic development, expedited the process of Trk inhibitor development. In the present review, the development processes of larotrectinib and entrectinib have been described, along with discussion on other Trk inhibitors currently in clinical trials. The on-target effects of Trk inhibitors in Trk signaling exhibit adverse effects on the central nervous system, such as withdrawal pain, weight gain, and dizziness. A next generation sequencing-based method has been approved for companion diagnostics of larotrectinib, which can detect various types of Trk fusions in tumor samples. With the adoption of the tissue-agnostic approach, the development of Trk inhibitors has been accelerated.

Yoon KB, et al. Immune Netw. 2016 Jun;16(3):183-188. https://doi.org/10.4110/in.2016.16.3.183

Recently, more than 30 small molecules and eight monoclonal antibodies that modulate kinase signaling have been approved for the treatment of several pathological conditions, including cancer, idiopathic pulmonary fibrosis, and rheumatoid arthritis. Among them, kinase modulators have been a primary focus for use in cancer treatment. Cellular senescence is believed to protect cells from tumorigenesis by irreversibly halting cell cycle progression and avoiding the growth of damaged cells and tissues. Senescence can also contribute to tumor suppression and be utilized as a mechanism by anti-cancer agents. Although the role of kinase modulators in cancer treatment and their effects on senescence in tumor development have been extensively studied, the relationship between kinase modulators for cancer treatment and senescence has not been fully discussed. In this review, we discuss the pro- and anti-tumorigenesis functions of senescence and summarize the key roles of kinase modulators in the regulation of senescence against tumors.