Abstract
The difficulty of early diagnosis and the development of drug resistance are two major barriers to the successful treatment of cancer. Autophagy plays a crucial role in several cellular functions, and its dysregulation is associated with both tumorigenesis and drug resistance. Unc-51-like kinase 1 (ULK1) is a serine/threonine kinase that participates in the initiation of autophagy. Many studies have indicated that compounds that directly or indirectly target ULK1 could be used for tumor therapy. However, reports of the therapeutic effects of these compounds have come to conflicting conclusions. In this work, we reviewed recent studies related to the effects of ULK1 on the regulation of autophagy and the development of drug resistance in cancers, with the aim of clarifying the mechanistic underpinnings of this therapeutic target.
Highlights
Cancer is one of the leading causes of death in humans [1]
We summarized the biological function of Unc-51-like kinase 1 (ULK1) in tumors with respect to its potential as a target for tumor therapy and its impact on the occurrence of drug resistance by mediating autophagy in tumor cells
BRAF inhibitors have been approved by the Food and Drug Administration, their therapeutic benefits prognosis, causing mortality rates to increase by 70% as compared with normal BRAF backgrounds for cancer patients with BRAF protein mutations are still not obvious [171]
Summary
Cancer is one of the leading causes of death in humans [1]. significant advances have been made in cancer research, the successful treatment of cancer still faces severe challenges [2]. On the other hand, develops during cancer treatment as an adaptation to selective pressure from the therapeutics These processes are related to the high expression of therapeutic targets and the activation of compensatory signaling pathways [10,11,12]. The inhibition of autophagy at this stage leads to the increase of intracellular reactive oxygen species, genomic dysfunction, and the accumulation of P62 protein These changes collectively result in an increase of ER pressure and DNA damage, and promote the formation of tumors [18]. It has been shown that ULK1 can either promote or inhibit tumor growth through protein–protein interactions and post-translational modification-mediated autophagy in nutrient-deficient environments [24] Both the positive and negative regulation of ULK can situationally protect tumor cells from excessive autophagy [25]. We summarized the biological function of ULK1 in tumors with respect to its potential as a target for tumor therapy and its impact on the occurrence of drug resistance by mediating autophagy in tumor cells
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