INTERNATIONAL CONGRESS OF
PharmacoGenetics
HSP27: A missing element in drug resistance in cancers
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Fereshteh Ebrahimi,1,*
1. 1. Zanjan Pharmaceutical Biotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran 2. Department of Medical Genetics and Molecular Medicine, School of Medicine, Zanjan university of Medical Sciences, Zanjan, Iran
- Introduction: HSP27, a member of the small heat shock protein family, holds a vital role in personalized medicine, particularly in cancer therapy. Its versatile properties have elevated it as a promising target for enhancing treatment effectiveness and reducing side effects. Despite advancements in treatment modalities like chemotherapy, radiotherapy, surgery, and the latest immunotherapy, cancer continues to stand as a primary global mortality cause. In the year 2020 alone, an estimated 19.3 million new cancer cases and 10 million cancer-related deaths were recorded. Although chemotherapy remains the prevailing cancer treatment, it fails to yield desired responses in some patients, primarily due to the emergence of drug resistance within tumors. Hence, investigating and unraveling the impactful mechanisms of drug resistance and formulating therapeutic strategies to combat it become imperative. Drug resistance can stem from various mechanisms, including alterations in drug absorption and expulsion, DNA damage repair, cellular apoptosis, tumor microenvironment influences, and genetic modifications. HSP27 emerges as a pivotal player influencing pharmacogenetic responses, particularly in cancer therapy, where its expression levels can dictate cellular susceptibility or resistance to diverse chemotherapeutic agents and targeted treatments.
- Methods: Data were collected by conducting to outline comprehensive studies published in PubMed, Web of science, Scopus and Google scholar databases from 2015 to 2024 by using keywords such as “HSP27”, “drug resistance”, “cancer”, “pharmacogenetic” and related combinations.
- Results: The review of findings highlights the significance of the HSP27 molecule in drug resistance and sensitivity mechanisms. HSP27 is associated with drug resistance in various cancers, inhibition of apoptosis, and promotion of cell survival. It is often overexpressed in tumors and provides protection against drugs like Doxorubicin by inhibiting senescence through p53 mediation, thus enabling cancer cells to evade treatment. In oncogene-addicted cancer cells, suppression of HSP27 can shift target factors from cytostatic to cytotoxic, enhancing apoptosis and drug efficacy. Additionally, significant increases in sensitivity to 5-Fluorouracil and Vincristine, and promotion of apoptosis and tumor growth inhibition, are observed upon reducing HSP27 in colon cancer cells. Inhibiting HSP27, especially through its phosphorylation, has shown potential in enhancing radiotherapy efficacy, as evident by decreased cell survival in cancer cell lines. Besides HSP27 acts as a negative regulator of apoptosis in glioblastoma, suggesting that its modulation could improve treatment outcomes.
- Conclusion: In summary, HSP27 plays a significant role in the development of drug resistance; however, its modulation can enhance drug sensitivity. While HSP27 presents opportunities for strengthening cancer therapies and safeguarding against treatment-related toxicity, its overexpression can also complicate treatment strategies, hence needs for precise examination in personalized medical approaches.
- Keywords: HSP27, Pharmacogenetic, Cancer, Drug resistance
