Abstract
Complications associated with advanced cancer are a major clinical challenge and, if associated with bone metastases, worsen the prognosis and compromise the survival of the patients. Breast and prostate cancer cells exhibit a high propensity to metastasize to bone. The bone microenvironment is unique, providing fertile soil for cancer cell propagation, while mineralized bone matrices store potent growth factors and cytokines. Biologically active transforming growth factor β (TGF-β), one of the most abundant growth factors, is released following tumor-induced osteoclastic bone resorption. TGF-β promotes tumor cell secretion of factors that accelerate bone loss and fuel tumor cells to colonize. Thus, TGF-β is critical for driving the feed-forward vicious cycle of tumor growth in bone. Further, TGF-β promotes epithelial-mesenchymal transition (EMT), increasing cell invasiveness, angiogenesis, and metastatic progression. Emerging evidence shows TGF-β suppresses immune responses, enabling opportunistic cancer cells to escape immune checkpoints and promote bone metastases. Blocking TGF-β signaling pathways could disrupt the vicious cycle, revert EMT, and enhance immune response. However, TGF-β’s dual role as both tumor suppressor and enhancer presents a significant challenge in developing therapeutics that target TGF-β signaling. This review presents TGF-β’s role in cancer progression and bone metastases, while highlighting current perspectives on the therapeutic potential of targeting TGF-β pathways.
Highlights
This study has indicated that low expression of Prostate transmembrane protein androgen induced 1 (PMEPA1) is associated with poor prognosis in breast and prostate cancer and can serve as a prognostic marker for bone metastases [123]
transforming growth factor β (TGF-β) has been identified as a key regulator of bone metastases owing to its function as a pluripotent cytokine in tumor, bone, and the immune system
TGF-β is a major regulator of tumorigenesis and TGF-β signaling is present in most cells, an ambiguous function of TGF-β as a tumor suppressor in early-stage tumors and a tumor enhancer in advanced cancer poses a challenge in developing therapeutics that target TGFβ for the treatment of breast and prostate cancer metastases
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Due to significant advancements in diagnosis and treatment, patients with bone metastases, from breast cancer and prostate cancer, can live longer after diagnosis They suffer from debilitating complications of skeletal-related events, which significantly increase morbidity [12]. For the past two decades, multiple strategies have been used to target TGF-β signaling pathway such as TGF-β receptor kinase inhibitors, TGF-β neutralizing antibodies, soluble receptor decoys, and TGF-β antisense oligonucleotides, which could inhibit TGF-β activity [19,20] These therapeutic strategies have successfully shown their benefit in in vitro studies and preclinical animal models. Due to increased bone resorption and increased TGF-β release restrained Th1 lineage development, and blocking TGF-β signaling together with immune checkpoint inhibitors could have better effects on regression of prostate cancer bone metastases [26]. Current studies and results from clinical trials it seems that synergistic therapeutic approach by combining TGF-β inhibitors with immunotherapy can have better therapeutic outcome in patients with bone metastases as highlighted in this review
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
