عنوان مقاله:

نویسندگان:

رحمان محمدی، فرزانه اقاسی، بیتا خاصی، امیرحسین رحیم بخش

ABSTRACT This review delves into the molecular mechanisms underlying drug resistance in cancer stem cells (CSCs) and the pivotal role of signaling pathways in this process. CSCs, with their unique characteristics such as self-renewal, long-term survival, and resistance to standard therapies, pose significant challenges in cancer treatment and are a major factor in tumor recurrence and progression. Key signaling pathways, including Wnt, Notch, Hedgehog, PI3K/Akt, and NF-κB, enhance drug resistance in CSCs by regulating cellular survival and self-renewal processes. Additionally, emerging pathways such as Hippo/YAP, NRF2, AXL/STAT3, and AMPK/mTOR also play significant roles in CSC drug resistance. The Hippo pathway, through YAP activation, promotes CSC stemness and survival. NRF2 enhances oxidative stress defense, AXL/STAT3 boosts survival and growth signaling, and AMPK/mTOR supports cellular survival by regulating metabolism and inducing dormancy under stress. Targeting these pathways offers new avenues for improving therapeutic efficacy in combating drug resistance and cancer recurrence. Furthermore, the tumor microenvironment (TME) and exosomes secreted by CSCs contribute to drug resistance by transferring resistance-inducing molecules and providing support to CSCs. This review, in addition to analyzing the underlying mechanisms, introduces novel approaches such as the use of monoclonal antibodies, signaling inhibitors, and engineered exosomes as drug carriers to reduce drug resistance and improve treatment efficacy. Findings indicate that precisely targeting CSCs and their associated signaling pathways can lead to better therapeutic outcomes, reduced cancer recurrence, and ultimately, improved quality of life for cancer patients. Further research on these emerging pathways could pave the way for more targeted and effective cancer therapies.

Keywords: Cancer stem cells (CSCs), Drug resistance, Signaling pathways, Tumor microenvironment (TME), Exosomes, Chemoresistance mechanisms

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محمدی، رحمان، اقاسی، فرزانه، خاصی، بیتا، رحیم بخش، امیرحسین، 1404، مکانیسم‌های مولکولی مقاومت دارویی در سلول‌های بنیادی سرطانی: هدف‌گیری مسیرهای سیگنالینگ برای افزایش کارایی درمان سرطان، کنگره بین المللی زیست پزشکی سرطان و سلولهای بنیادی، http://conf.sums.ac.ir/fa/archive_index.php?c=HN-icsbc1&aid=1514231