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.
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http://dx.doi.org/10.3390/cancers12020352 | DOI Listing |
Mol Cancer
January 2025
Department of Radiation Oncology, Peking University Third Hospital, Beijing, 100191, China.
Background: Sorafenib, an FDA-approved drug for advanced hepatocellular carcinoma (HCC), faces resistance issues, partly due to myeloid-derived suppressor cells (MDSCs) that enhance immunosuppression in the tumor microenvironment (TME).
Methods: Various murine HCC cell lines and MDSCs were used in a series of in vitro and in vivo experiments. These included subcutaneous tumor models, cell viability assays, flow cytometry, immunohistochemistry, and RNA sequencing.
Cancer Cell Int
January 2025
Department of Toxicology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
Background: Cancer remains a leading cause of death worldwide. Environmental factors, specifically endocrine-disrupting chemicals (EDCs), like phthalates, are increasingly being linked to cancer development. Phthalates, widely used in consumer products, can activate the aryl hydrocarbon receptor (AhR).
View Article and Find Full Text PDFVirol J
January 2025
Virology Laboratory, Faculty of Life Sciences and Biotechnology, South Asian University (SAU), New Delhi, 110068, India.
Maturation inhibitors (MIs) block HIV-1 maturation by preventing the cleavage of the capsid protein and spacer peptide 1 (CA-SP1). Bevirimat (BVM), a first-in-class MI, displayed sub-optimal efficacy in clinical trials due to presence of SP1:V7A polymorphism in the Gag protein.This polymorphism is inherently present in HIV-1 subtype C and conferred resistance to BVM.
View Article and Find Full Text PDFItal J Pediatr
January 2025
Department of Neonatology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Henan, China.
Background: Severe pulmonary infection is the primary cause of death in children aged < 5 years. The early identification of pathogenic bacteria and targeted anti-infective therapies can significantly improve the prognosis of children with severe infections. This study aims to provide a reference for the rational use of antibiotics at an early stage in children with severe pulmonary infections.
View Article and Find Full Text PDFBMC Microbiol
January 2025
Department of Infectious Disease Epidemiology, Robert Koch Institute (RKI), Berlin, Germany.
Background: Carbapenem-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA) are among WHO's priority pathogens with antimicrobial resistance (AMR). Studies suggest potential impacts of the COVID-19-pandemic on AMR. We described changes in AMR incidence and epidemiology in Germany during the COVID-19-pandemic.
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