Current Pharmaceutical Design - Volume 26, Issue 17, 2020

G protein-coupled receptors (GPCRs) are highly expressed on a variety of tumour tissues while several GPCR exogenous ligands become marketed pharmaceuticals. In recent decades, cancer stem cells (CSCs) become widely investigated drug targets for cancer therapy but the underlying mechanism is still not fully elucidated. There are vigorous participations of GPCRs in CSCs-related signalling and functions, such as biomarkers for CSCs, activation of Wnt, Hedgehog (HH) and other signalling to facilitate CSCs progressions. This relationship can not only uncover a novel molecular mechanism for GPCR-mediated cancer cell functions but also assist our understanding of maintaining and modulating CSCs. Moreover, GPCR antagonists and monoclonal antibodies could be applied to impair CSCs functions and consequently attenuate tumour growth, some of which have been undergoing clinical studies and are anticipated to turn into marketed anticancer drugs. Therefore, this review summarizes and provides sufficient evidences on the regulation of GPCR signalling in the maintenance, differentiation and pluripotency of CSCs, suggesting that targeting GPCRs on the surface of CSCs could be potential therapeutic strategies for cancer therapy.

Renal cell carcinoma (RCC) is an intractable genitourinary malignancy that accounts for approximately 4% of adult malignancies. Currently, there is no approved targeted therapy for RCC that has yielded durable remissions, and they remain palliative in intent. Emerging evidence has indicated that renal tumorigenesis and RCC treatment-resistance may originate from renal cancer stem cells (CSCs) with tumor-initiating capacity (CSC hypothesis). A better understanding of the mechanism underlying renal CSCs will help to dissect RCC heterogeneity and drug treatment efficiency, to promote more personalized and targeted therapies. In this review, we summarized the stem cell characteristics of renal CSCs. We outlined the targeting strategies and challenges associated with developing therapies that target renal CSCs angiogenesis, immunosuppression, signaling pathways, surface biomarkers, microRNAs and nanomedicine. In conclusion, CSCs are an important role in renal carcinogenesis and represent a valid target for treatment of RCC patients.

Cancer stem cells (CSCs), also known as tumor-initiating cells, are a sub-population of tumor cells found in many human cancers that are endowed with self-renewal and pluripotency. CSCs may be more resistant to conventional anticancer therapies than average cancer cells, as they can easily escape the cytotoxic effects of standard chemotherapy, thereby resulting in tumor relapse. Despite significant progress in related research, effective elimination of CSCs remains an unmet clinical need. CSCs are localized in a specialized microenvironment termed the niche, which plays a pivotal role in cancer multidrug resistance. The niche components of CSCs, such as the extracellular matrix, also physically shelter CSCs from therapeutic agents. Colorectal cancer is the most common malignancy worldwide and presents a relatively transparent process of cancer initiation and development, making it an ideal model for CSC niche research. Here, we review recent advances in the field of CSCs using colorectal cancer as an example to illustrate the potential therapeutic value of targeting the CSC niche. These findings not only provide a novel theoretical basis for in-depth discussions on tumor occurrence, development, and prognosis evaluation, but also offer new strategies for the targeted treatment of cancer.

Cancer stem cells (CSCs) show self-renewal ability and multipotential differentiation, like normal stem or progenitor cells, and which proliferate uncontrollably and can escape the effects of drugs and phagocytosis by immune cells. Traditional monotherapies, such as surgical resection, radiotherapy and chemotherapy, cannot eradicate CSCs, however, combination therapy may be more effective at eliminating CSCs. The present review summarizes the characteristics of CSCs and several promising combination therapies to eradicate them.

Accumulating evidences have demonstrated that the existence of breast cancer-initiating cells, which drives the original tumorigenicity, local invasion and migration propensity of breast cancer. These cells, termed as breast cancer stem cells (BCSCs), possess properties including self-renewal, multidirectional differentiation and proliferative potential, and are believed to play important roles in the intrinsic drug resistance of breast cancer. One of the reasons why BCBCs cause difficulties in breast cancer treating is that BCBCs can control both genetic and non-genetic elements to keep their niches safe and sound, which allows BCSCs for constant self-renewal and differentiation. Therapeutic strategies designed to target BCSCs may ultimately result in effective interventions for the treatment of breast cancer. Novel strategies including nanomedicine, oncolytic virus therapy, immunotherapy and induced differentiation therapy are emerging and proved to be efficient in anti-BCSCs therapy. In this review, we summarized breast tumor biology and the current challenges of breast cancer therapies, focused on breast cancer stem cells, and introduced promising therapeutic strategies targeting BCSCs.

Mesenchymal stem cells (MSCs) are a kind of adult stem cells with self-replication and multidirectional differentiation, which can differentiate into tissue-specific cells under physiological conditions, maintaining tissue self-renewal and physiological functions. They play a role in the pathological condition by lateral differentiation into tissue-specific cells, replacing damaged tissue cells by playing the role of a regenerative medicine , or repairing damaged tissues through angiogenesis, thereby, regulating immune responses, inflammatory responses, and inhibiting apoptosis. It has become an important seed cell for tissue repair and organ reconstruction, and cell therapy based on MSCs has been widely used clinically. The study found that the probability of stem cells migrating to the damaged area after transplantation or differentiating into damaged cells is very low, so the researchers believe the leading role of stem cell transplantation for tissue repair is paracrine secretion, secreting growth factors, cytokines or other components. Exosomes are biologically active small vesicles secreted by MSCs. Recent studies have shown that they can transfer functional proteins, RNA, microRNAs, and lncRNAs between cells, and greatly reduce the immune response. Under the premise of promoting proliferation and inhibition of apoptosis, they play a repair role in tissue damage, which is caused by a variety of diseases. In this paper, the biological characteristics of exosomes (MSCs-exosomes) derived from mesenchymal stem cells, intercellular transport mechanisms, and their research progress in the field of stem cell therapy are reviewed.

Urological cancer refers to cancer in organs of the urinary system and the male reproductive system. It mainly includes prostate cancer, bladder cancer, renal cancer, etc., seriously threatening patients’ survival. Although there are many advances in the treatment of urological cancer, approved targeted therapies often result in tumor recurrence and therapy failure. An increasing amount of evidence indicated that cancer stem cells (CSCs) with tumor-initiating ability were the source of treatment failure in urological cancer. The development of CSCstargeted strategy can provide a possibility for the complete elimination of urological cancer. This review is based on a search of PubMed, Google scholar and NIH database (http://ClinicalTrials.gov/) for English language articles containing the terms: “biomarkers”, “cancer stem cells”, “targeting/targeted therapy”, “prostate cancer”, bladder cancer” and “kidney cancer”. We summarized the biomarkers and stem cell features of the prostate, bladder and renal CSCs, outlined the targeted strategies for urological CSCs from signaling pathways, cytokines, angiogenesis, surface markers, elimination therapy, differentiation therapy, immunotherapy, microRNA, nanomedicine, etc., and highlighted the prospects and future challenges in this research field.

The innate abilities of cancer stem cells (CSCs), such as multi-drug resistance, drug efflux, quiescence and ionizing radiation tolerance, protect them from most traditional chemotherapeutics. As a result, this small subpopulation of persistent cells leads to more aggressive and chemoresistant cancers, causing tumour relapse and metastasis. This subpopulation is differentiated from the bulk tumour population through a wide variety of surface markers expressed on the cell surface. Recent developments in nanomedicine and targeting delivery methods have given rise to new possibilities for specifically targeting these markers and preferentially eliminating CSCs. Herein, we first summarize the range of surface markers identifying CSC populations in a variety of cancers; then, we discuss recent attempts to actively target CSCs and their niches using liposomal, nanoparticle, carbon nanotube and viral formulations.