Abstract
Cellular senescence is a permanent blockade of cell proliferation. In response to therapy-induced stress, cancer cells undergo apoptosis or premature senescence. In apoptosis-resistant cancer cells or at lower doses of anticancer drugs, therapy-induced stress leads to premature senescence. The role of this senescence in cancer treatment is discussable. First of all, the senescent cells lose the ability to proliferate, migrate, and invade. In addition, the senescent cells secrete a set of proteins (inflammatory cytokines, chemokines, growth factors) known as the senescence-associated secretory phenotype (SASP), which influences non-senescent normal cells and non-senescent cancer cells in the tumor microenvironment and triggers tumor promotion and recurrence. Recently, many studies have examined senescence induction through breast cancer therapy and potentially using this phenomenon to treat this cancer. This review summarizes the recent in vitro, in vivo, and clinical studies investigating senescence in breast cancer treatments. Senescence inductors, senolytics, as well as their action mechanism are discussed herein. Potential SASP-modulating treatment strategies are also described.
Highlights
SN-38, an active metabolite of camptothecin, induces senescence after the treatment of MCF-7 cells. It was demonstrated upon treatment by observation of large, flattened SA-β-gal-positive cells, resistant to apoptosis. The mechanism of this activity was not investigated in breast cancer; the studies of Shamanna and Opresko revealed some rationale for its consideration, such as camptothecin, and the ability to drive breast cancer cells into senescence in Werner syndrome protein (WRN) dependent manner
Cerrito et al showed that vinorelbine and 5-fluorouracil combined treatment can induce senescence, autophagic cell death, and apoptosis, and all those processes can be regarded as an anticancer mechanism in MDA-MB-231 cells
Premature senescence is an inherent outcome of breast cancer treatment strategy, as well as an element of novel strategies that rely on applying phytochemicals or targeted therapy
Summary
Breast cancer is the most commonly diagnosed type of malignancy in females. A commonly exploited subtype classification of breast cancer was based on gene expression analysis. It includes luminal A, luminal B, HER2-enriched, and basal-like subtypes [2,3]. The effect of surgical resection can be enhanced via neoadjuvant or adjuvant systemic therapy. This includes hormonotherapy, chemotherapy, and targeted therapy [6]. Anty-HER therapy (humanized monoclonal antibodies and small kinase inhibitors ) + chemotherapy luminal B. Recently other mechanisms of anticancer drug activity such as induction of autophagy or premature senescence are implicated in malignant cell death [7]
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