The Hedgehog pathway is essential for embryonic development but also for tissue and organ homeostasis in adult organisms. Activation of this pathway leads to the expression of target genes involved in proliferation, angiogenesis and stem cell self-renewal. Moreover, abnormal persistence of Hedgehog signaling is directly involved in a wide range of human cancers. Development of novel strategies targeting the Hedgehog pathway has become a subject of increased interest in anticancer therapy. These data are sustained by pre-clinical studies demonstrating that Hedgehog pathway inhibitors could represent an effective strategy against a heterogeneous panel of malignancies. Limited activity in other tumor types could be explained by the existence of crosstalk between the Hedgehog pathway and other signaling pathways that can compensate for its function. This review describes the Hedgehog pathway in detail, with its physiological roles during embryogenesis and adult tissues, and summarizing the preclinical evidence on its inhibition, the crosstalk between Hedgehog and other cancer-related pathways and finally the potential therapeutic effects of emerging compounds.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.phrs.2019.01.014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Noncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells.
Sci Adv
January 2025
Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
The unfolded protein response (UPR) pathway is crucial for tumorigenesis, mainly by regulating cancer cell stress responses and survival. However, whether UPR factors facilitate cell-cell communication between cancer cells and immune cells to drive cancer progression remains unclear. We found that adenosine 3',5'-monophosphate response element-binding protein 3-like protein 2 (CREB3L2), a noncanonical UPR factor, is overexpressed and activated in triple-negative breast cancer, where its cleavage releases a C-terminal fragment that activates the Hedgehog pathway in neighboring CD8+ T cells.
View Article and Find Full Text PDFEmerging Combinatorial Drug Delivery Strategies for Breast Cancer: A Comprehensive Review.
Curr Drug Targets
January 2025
Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar (M.P.) 470003, India.
Breast cancer remains the second most prevalent cancer among women in the United States. Despite advancements in surgical, radiological, and chemotherapeutic techniques, multidrug resistance continues to pose significant challenges in effective treatment. Combination chemotherapy has emerged as a promising approach to address these limitations, allowing multiple drugs to target malignancies via distinct mechanisms of action.
View Article and Find Full Text PDFmiR-28-3p suppresses gastric cancer growth and EMT-driven metastasis by targeting the ARF6/Hedgehog axis.
Mol Cell Probes
January 2025
Department of Medical Oncology, The First People's Hospital of Yunnan Province/The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650000, China; Faculty of Medicine, Kunming University of Science and Technology, Kunming, 650000, China. Electronic address:
Gastric cancer (GC), among the most prevalent malignant tumors globally, demonstrates a rapid metastasis rate leading to high mortality. While microRNAs (miRNAs) have been recognized as critical regulators of tumor progression, the specific role of miR-28-3p in GC remains unclear. In this study, we demonstrate that miR-28-3p acts as a tumor suppressor by inhibiting GC cell proliferation and EMT-driven migration in vitro, as well as tumor growth and metastasis in vivo.
View Article and Find Full Text PDFNon-cell-autonomous regulation of mTORC2 by Hedgehog signaling maintains lipid homeostasis.
Cell Rep
January 2025
Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Integrative Program for Biological and Genome Sciences, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:
Organisms allocate energetic resources between essential cellular processes to maintain homeostasis and, in turn, maximize fitness. The nutritional regulators of energy homeostasis have been studied in detail; however, how developmental signals might impinge on these pathways to govern metabolism is poorly understood. Here, we identify a non-canonical role for Hedgehog (Hh), a classic regulator of development, in maintaining intestinal lipid homeostasis in Caenorhabditis elegans.
View Article and Find Full Text PDFPrimary Cilia Formation Mediated by Hsa_Circ_0005185/OTUB1/RAB8A Complex Inhibits Prostate Cancer Progression by Suppressing Hedgehog Signaling Pathway.
Adv Sci (Weinh)
January 2025
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200030, China.
Prostate cancer (PCa) is one of the most common malignancies for male individuals globally. Androgen deprivation therapy (ADT) initially demonstrated significant efficacy in treating PCa; however, most cases of PCa eventually progress to castration-resistant prostate cancer (CRPC), which becomes increasingly challenging to manage. Notably, the loss or disruption of primary cilia in PCa cells may play a critical role in the progression of the disease, and there are no reports on the role of circular RNAs in ciliogenesis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!