Abstract
Despite some significant advancements, breast cancer has become the most prevalent cancer in the world. One of the main reasons for failure in treatment and metastasis has been attributed to the presence of cancer initiating cells—cancer stem cells. Consequently, research is now being focussed on targeting cancer cells along with their stem cell population. Non-oncology drugs are gaining increasing attention for their potent anticancer activities. Metformin, a drug commonly used to treat type 2 diabetes, is the best example in this regard. It exerts its therapeutic action by activating 5′ adenosine monophosphate-activated protein kinase (AMPK). Activated AMPK subsequently phosphorylates and targets several cellular pathways involved in cell growth and proliferation and the maintenance of stem-like properties of cancer stem cells. Therefore, AMPK is emerging as a target of choice for developing effective anticancer drugs. Vanadium compounds are well-known PTP inhibitors and AMPK activators. They find extensive applications in treatment of diabetes and obesity via PTP1B inhibition and AMPK-mediated inhibition of adipogenesis. However, their role in targeting cancer stem cells has not been explored yet. This review is an attempt to establish the applications of insulin mimetic vanadium compounds for the treatment of breast cancer by AMPK activation and PTP1B inhibition pathways.
Highlights
Breast cancer is the most common cancer in women of all races across the globe.According to the World Health Organization, 2.3 million women were diagnosed with breast cancer in 2020 alone, with approximately 685,000 deaths reported globally
The phosphorylation and activation of AMPK have several implications that result in reduced cell proliferation and apoptosis in cancer cells
Activated AMPK phosphorylates several downstream substrates resulting in downregulation of cyclins, cell cycle arrest, suppression of fatty acid, cholesterol, triglyceride syntheses, inhibition of the Mammalian Target of the Rapamycin (mTOR) pathway and induction of autophagy and Warburg effect antagonism
Summary
Breast cancer is the most common cancer in women of all races across the globe. According to the World Health Organization, 2.3 million women were diagnosed with breast cancer in 2020 alone, with approximately 685,000 deaths reported globally. In vitro studies using breast cancer stem cell markers reveal that BCSCs are relatively resistant to radiation therapy and chemotherapy This was resonated in clinical studies, wherein molecular profiles of tumours treated with chemotherapy closely resembled the gene profiling of CD44+CD24− cells [13]. This resistance is imparted by stem cell specific pathways such as Wnt/β–catenin, Notch, and Hedgehog signalling. These pathways are often dysregulated in breast cancer and, various approaches are being designed to target them for effective treatment [11]. Clinical trials have been initiated using combination therapies targeting the canonical Wnt signalling pathway (ClinicalTrials.gov Identifier: NCT01351103) as well as Hedgehog signalling pathways (ClinicalTrials.gov Identifier: NCT02694224)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
