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The Role of Cancer Stem Cells in Colorectal Cancer: From the Basics to Novel Clinical Trials.

ABSTRACT: The treatment options available for colorectal cancer (CRC) have increased over the years and have significantly improved the overall survival of CRC patients. However, the response rate for CRC patients with metastatic disease remains low and decreases with subsequent lines of therapy. The clinical management of patients with metastatic CRC (mCRC) presents a unique challenge in balancing the benefits and harms while considering disease progression, treatment-related toxicities, drug resistance and the patient's overall quality of life. Despite the initial success of therapy, the development of drug resistance can lead to therapy failure and relapse in cancer patients, which can be attributed to the cancer stem cells (CSCs). Thus, colorectal CSCs (CCSCs) contribute to therapy resistance but also to tumor initiation and metastasis development, making them attractive potential targets for the treatment of CRC. This review presents the available CCSC isolation methods, the clinical relevance of these CCSCs, the mechanisms of drug resistance associated with CCSCs and the ongoing clinical trials targeting these CCSCs. Novel therapeutic strategies are needed to effectively eradicate both tumor growth and metastasis, while taking into account the tumor microenvironment (TME) which plays a key role in tumor cell plasticity.

SUBMITTER: Hervieu C

PROVIDER: S-EPMC7961892 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Pitfalls in RECIST Data Extraction for Clinical Trials: Beyond the Basics.

Project description:Response Evaluation Criteria in Solid Tumors (RECIST) is a standardized methodology for determining therapeutic response to anticancer therapy using changes in lesion appearance on imaging studies. Many radiologists are now using RECIST in their routine clinical workflow, as part of consultative arrangements, or within dedicated imaging core laboratories. Although basic RECIST methodology is well described in published articles and online resources, inexperienced readers may encounter difficulties with certain nuances and subtleties of RECIST. This article illustrates a set of pitfalls in RECIST assessment considered to be "beyond the basics." These pitfalls were uncovered during a quality improvement review of a recently established cancer imaging core laboratory staffed by radiologists with limited prior RECIST experience. Pitfalls are presented in four categories: (1) baseline selection of lesions, (2) reassessment of target lesions, (3) reassessment of nontarget lesions, and (4) identification of new lesions. Educational and operational strategies for addressing these pitfalls are suggested. Attention to these pitfalls and strategies may improve the overall quality of RECIST assessments performed by radiologists.

| S-EPMC4429002 | biostudies-literature

NFATC2 is a novel therapeutic target for colorectal cancer stem cells.

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| S-EPMC6199214 | biostudies-literature

Clinical trials update: Tertiary prevention of colorectal cancer.

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Stem Cells in Clinical Trials on Neurological Disorders: Trends in Stem Cells Origins, Indications, and Status of the Clinical Trials.

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Clinical trials using dental stem cells: 2022 update.

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| S-EPMC4397514 | biostudies-other

Targeting Colorectal Cancer Stem Cells as an Effective Treatment for Colorectal Cancer.

Project description:As one of the common cancers that threaten human life, the recurrence and metastasis of colorectal cancer seriously affect the prognosis of patients. Although new drugs and comprehensive treatments have been adopted, the current treatment effect on this tumor, especially in advanced colorectal cancer, is still not satisfactory. More and more evidence shows that tumors are likely to be a stem cell disease. In recent years, the rise of cancer stem cell theory has provided a new way for cancer treatment. Studies have found that a small number of special cells in colorectal cancer tissues that induce tumorigenesis, proliferation, and promote tumor migration and metastasis, namely, colorectal cancer stem cells. Colorectal cancer stem cells are defined with a group of cell-surface markers, such as CD44, CD133, CD24, epithelial cell adhesion factor molecule, LGR5, and acetaldehyde dehydrogenase. They are highly tumorigenic, aggressive, and chemoresistant and thus are critical in the metastasis and recurrence of colorectal cancer. Therefore, targeting colorectal cancer stem cells may become an important research direction for the future cure of colorectal cancer.

| S-EPMC7785997 | biostudies-literature

Colorectal Cancer Stem Cells and Targeted Agents.

Project description:Since their discovery, cancer stem cells have become a hot topic in cancer therapy research. These cells possess stem cell-like self-renewal and differentiation capacities and are important factors that dominate cancer metastasis, therapy-resistance and recurrence. Worse, their inherent characteristics make them difficult to eliminate. Colorectal cancer is the third-most common cancer and the second leading cause of cancer death worldwide. Targeting colorectal cancer stem cells (CR-CSCs) can inhibit colorectal cancer metastasis, enhance therapeutic efficacy and reduce recurrence. Here, we introduced the origin, biomarker proteins, identification, cultivation and research techniques of CR-CSCs, and we summarized the signaling pathways that regulate the stemness of CR-CSCs, such as Wnt, JAK/STAT3, Notch and Hh signaling pathway. In addition to these, we also reviewed recent anti-CR-CSC drugs targeting signaling pathways, biomarkers and other regulators. These will help researchers gain insight into the current agents targeting to CR-CSCs, explore new cancer drugs and propose potential therapies.

| S-EPMC10748092 | biostudies-literature

Cancer stem cells from colorectal cancer-derived cell lines.

Project description:Cancer stem cells (CSCs) are the subpopulation of cells within a tumor that can self-renew, differentiate into multiple lineages, and drive tumor growth. Here we describe a two-pronged approach for the identification and characterization of CSCs from colorectal cancer cell lines, using a Matrigel-based differentiation assay, and cell surface markers CD44 and CD24. About 20 to 30% of cells from the SW1222 cell line form megacolonies in Matrigel that have complex 3D structures resembling colonic crypts. The megacolonies' capacity to self-renew in vitro is direct evidence that they contain the CSCs. Furthermore, just 200 cells from SW1222 megacolonies initiate tumors in NOD/SCID mice. We also showed that CD44(+)CD24(+) cells enriched for colorectal CSCs in the HT29 and SW1222 cell lines, which can self-renew and reform all four CD44/CD24 subpopulations, are the most clonogenic in vitro and can initiate tumors in vivo. A single SW1222 CD44(+)CD24(+) CSC, when grown in Matrigel, can form large megacolonies that differentiate into enterocyte, enteroendocrine, and goblet cell lineages. The HCT116 line does not differentiate or express CDX1, nor does it contain subpopulations of cells with greater tumor-forming capacity, suggesting that HCT116 contains mainly CSCs. However, forced expression of CDX1 in HCT116 leads to reduced clonogenicity and production of differentiating crypt-containing colonies, which can explain the selection for reduced CDX1 expression in many colorectal cancers. In summary, colorectal cancer cell lines contain subpopulations of CSCs, characterized by their cell surface markers and colony morphology, which can self-renew and differentiate into multiple lineages.

| S-EPMC2840416 | biostudies-literature

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Project description:The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising in contrast to the decreasing incidence of carcinomas in other subsites of the head and neck, in spite of the reduced prevalence of smoking. Human papilloma virus (HPV) infection, and in particular type 16 (HPV-16), is now recognized as a significant player in the onset of HPV positive OPSCC, with different epidemiological, clinical, anatomical, radiological, behavioural, biological and prognostic characteristics from HPV negative OPSCC. Indeed, the only subsite in the head and neck with a demonstrated aetiological viral link is, at present, the oropharynx. These observations lead to questions regarding management choices for patients based on tumour HPV status with important consequences on treatment, and on the role of vaccines and targeted therapy over the upcoming years.

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