Novel therapeutic agents introduced over the past decade, including immune checkpoint inhibitors and targeted therapies, have revolutionized the management of metastatic melanoma and significantly improved patient outcomes. Although robust and durable responses have been noted in some cases, treatment is often limited by innate or acquired resistance to these agents. This article provides an overview of known and suspected mechanisms involved with acquired resistance to BRAF/MEK inhibitors as well as developing insights into innate and acquired resistance to checkpoint inhibitors in patients with melanoma.
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http://dx.doi.org/10.1016/j.hoc.2020.09.005 | DOI Listing |
Cell Commun Signal
January 2025
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.
Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), is the leading cause of mortality from gynecological malignancies worldwide. Despite the initial effectiveness of treatment, acquired resistance to poly(ADP-ribose) polymerase inhibitors (PARPis) represents a major challenge for the clinical management of HGSOC, highlighting the necessity for the development of novel therapeutic strategies. This study investigated the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a pivotal regulator of glycolysis, in PARPi resistance and explored its potential as a therapeutic target to overcome PARPi resistance.
View Article and Find Full Text PDFNat Commun
January 2025
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
Evidence has shown that T-cell receptors (TCRs) that recognize the same epitopes may not be the exact TCR clonotypes but have slightly different TCR sequences. However, the changes in the genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined the evolutionary features in circulating TCR clonotypes observed in tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing of longitudinal blood samples and TCR sequencing of tumor tissue from a patient treated with anti-cytotoxic T-lymphocyte-associated protein 4/programmed cell death protein-1 therapy.
View Article and Find Full Text PDFMicrob Pathog
January 2025
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:
Following a period of disuse owing to the emergence of multidrug-resistant Gram-negative bacteria, colistin has regained global attention as an antibiotic of last resort. The resurgence in its utilization has led to a concurrent increase in acquired resistance, presenting a significant challenge in clinical treatment. Predominantly, resistance mechanisms involve alterations in the lipid A component of the lipopolysaccharide (LPS) structure.
View Article and Find Full Text PDFEnviron Pollut
January 2025
Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China.
Airborne microorganisms in hospitals present significant health risks to both patients and employees. However, their pollution profiles and associated hazards in different hospital areas remained largely unknown during the extensive use of masks and disinfectants. This study investigated the characteristics of bioaerosols in an urban general hospital during the COVID-19 pandemic and found that airborne bacteria and fungi concentrations range from 87±35 to 1037±275 CFU/m and 21±15 to 561±132 CFU/m, respectively, with the outpatient clinic and internal medicine ward showing the highest levels.
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