Drug-tolerant persister (DTP) cell populations were originally discovered in antibiotic-resistant bacterial biofilms. Similar populations with comparable features have since been identified among cancer cells and have been linked with treatment resistance that lacks an underlying genomic alteration. Research over the past decade has improved our understanding of the biological roles of DTP cells in cancer, although clinical knowledge of the role of these cells in treatment resistance remains limited. Nonetheless, targeting this population is anticipated to provide new treatment opportunities. In this Perspective, we aim to provide a clear definition of the DTP phenotype, discuss the underlying characteristics of these cells, their biomarkers and vulnerabilities, and encourage further research on DTP cells that might improve our understanding and enable the development of more effective anticancer therapies.
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http://dx.doi.org/10.1038/s41571-023-00815-5 | DOI Listing |
Front Med
January 2025
Zhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Jiaxing, 314400, China.
Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy.
View Article and Find Full Text PDFCancer Res
January 2025
Medical Department of Hematology, Oncology and Tumor Immunology, Molekulares Krebsforschungszentrum - MKFZ, Campus Virchow Klinikum, Charité - Universitätsmedizin, Berlin, Germany.
Redox Biol
December 2024
Cell and Tumor Biology, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India. Electronic address:
A significant clinical challenge in patients with colorectal cancer (CRC), which adversely impacts patient survival, is the development of therapy resistance leading to a relapse. Therapy resistance and relapse in CRC is associated with the formation of lipid droplets (LD) by stimulating de novo lipogenesis (DNL). However, the molecular mechanisms underlying the increase in DNL and the susceptibility to DNL-targeted therapies remain unclear.
View Article and Find Full Text PDFTransl Cancer Res
November 2024
Medical Oncology Centre, Saalfeld, Germany.
Non-small cell lung cancer (NSCLC) represents over 80% of lung cancer cases and has a high mortality worldwide, however, targeting common epidermal growth-factor receptor (EGFR) alterations (i.e., del19, L858R) has provided a paradigm shift in the treatment of NSCLC.
View Article and Find Full Text PDFCancer Metab
December 2024
Department of Medicine, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
Background: The efficacy of tyrosine kinase inhibitors (TKIs) targeting the EGFR is limited due to the persistence of drug-tolerant cell populations, leading to therapy resistance. Non-genetic mechanisms, such as metabolic rewiring, play a significant role in driving lung cancer cells into the drug-tolerant state, allowing them to persist under continuous drug treatment.
Methods: Our study employed a comprehensive approach to examine the impact of the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) on the adaptivity of lung cancer cells to EGFR TKI therapies.
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