Triple negative breast cancer (TNBC) is classically treated with combination chemotherapies. Although, initially responsive to chemotherapies, TNBC patients frequently develop drug-resistant, metastatic disease. Chemotherapy resistance can develop through many mechanisms, including induction of a transient growth-arrested state, known as the therapy-induced senescence (TIS). In this paper, we will focus on chemoresistance in TNBC due to TIS. One of the key characteristics of senescent cells is a complex secretory phenotype, known as the senescence-associated secretory proteome (SASP), which by prompting immune-mediated clearance of senescent cells maintains tissue homeostasis and suppresses tumorigenesis. However, in cancer, particularly with TIS, senescent cells themselves as well as SASP promote cellular reprograming into a stem-like state responsible for the emergence of drug-resistant, aggressive clones. In addition to chemotherapies, outcomes of recently approved immune and DNA damage-response (DDR)-directed therapies are also affected by TIS, implying that this a common strategy used by cancer cells for evading treatment. Although there has been an explosion of scientific research for manipulating TIS for prevention of drug resistance, much of it is still at the pre-clinical stage. From an evolutionary perspective, cancer is driven by natural selection, wherein the fittest tumor cells survive and proliferate while the tumor microenvironment influences tumor cell fitness. As TIS seems to be preferred for increasing the fitness of drug-challenged cancer cells, we will propose a few tactics to control it by using the principles of evolutionary biology. We hope that with appropriate therapeutic intervention, this detrimental cellular fate could be diverted in favor of TNBC patients.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264500 | PMC |
http://dx.doi.org/10.3389/fonc.2021.674354 | DOI Listing |
Front Immunol
December 2024
Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8 T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults.
View Article and Find Full Text PDFJOR Spine
December 2024
Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester, Manchester Academic Health Sciences Centre Manchester UK.
Background: Notochordal cells (NCs) present in the nucleus pulposus (NP) of the developing human intervertebral disc (IVD) disappear during the first decade of life. This loss coincides with the onset of IVD degeneration, therefore these cells are hypothesized to be important in NP homeostasis. Putative NC-derived (CD24) and progenitor (TIE2/GD2) cell sub-populations have previously been identified in the adult human NP, but their characteristics have yet to be compared.
View Article and Find Full Text PDFFront Med (Lausanne)
December 2024
Metabolismo Óseo, Vascular y Enfermedades Inflamatorias Crónicas, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
Introduction: Cardiovascular disease is the major cause of premature death in chronic kidney disease (CKD) and vascular damage is often detected belatedly, usually evaluated by expensive and invasive techniques. CKD involves specific risk factors that lead to vascular calcification and atherosclerosis, where inflammation plays a critical role. However, there are few inflammation-related markers to predict vascular damage in CKD.
View Article and Find Full Text PDFRegen Ther
March 2025
Department of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, PR China.
Dermal white adipose tissue (dWAT), distinguished by its origin from cells within the dermis and independence from subcutaneous fat tissue, has garnered significant attention for its non-metabolic functions. Characterized by strong communication with other components of the skin, dWAT mediates the proliferation and recruitment of various cell types by releasing adipogenic and inflammatory factors. Here, we focus on the modulatory role of dWAT at different stages during wound healing, highlighting its ability to mediate the adipocyte-to-myofibroblast transition which plays a pivotal role in the physiology and pathology processes of skin fibrosis, scarring, and aging.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P. R. China.
Anaplastic thyroid cancer (ATC) is the most lethal tumor arising from thyroid follicular epithelium. Lenvatinib is an off-label use option for ATC patients in many countries but an approved prescription in Japan. However, lenvatinib resistance is a substantial clinical challenge.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!