Ablation of Cancer Stem Cells by Therapeutic Inhibition of the MDM2–p53 Interaction in Mucoepidermoid Carcinoma

264

139

p21 functions as a cell cycle inhibitor and anti-proliferative effector in normal cells, and is dysregulated in some cancers. Earlier observations on p21 knockout models emphasized the role of this protein in cell cycle arrest under the p53 transcription factor activity. Although tumor-suppressor function of p21 is the most studied aspect of this protein in cancer, the role of p21 in phenotypic plasticity and its oncogenic/anti-apoptotic function, depending on p21 subcellular localization and p53 status, have been under scrutiny recently. Basic science and translational studies use precision gene editing to manipulate p21 itself, and proteins that interact with it; these studies have led to regulatory/functional/drug sensitivity discoveries as well as therapeutic approaches in cancer field. In this review, we will focus on targeting p21 in cancer research and its potential in providing novel therapies.

Section: P21 As a Target In Cancer Treatmentmentioning

confidence: 99%

p21 in Cancer Research

Shamloo

Usluer

2019

264

139

“…Inhibition of the MDM2-p53 interaction reduces ALDH high and CD44 high CSCs in mucoepidermoid carcinoma. A marked decrease in expression of Bmi-1 and in a fraction of ALDH high CD44 high was demonstrated in this model [38]. Rapid tumorigenesis was associated with the surface expression of PD-L1, E-cadherin, CD24, and VEGFR2 in epithelial CSCs, which was established from the ascites of a bladder cancer patient.…”

Section: Surface Receptors On Cscsmentioning

confidence: 94%

Recent Advances in Cancer Stem Cell-Targeted Immunotherapy

Badrinath

Yoo

2019

Cancer stem cells (CSCs) are one of the reasons for the relapse of cancer cells and metastasis. They have drug resistance against most chemotherapeutic agents. CSCs are also responsible for tumor cell heterogeneity and cause minimal residual disease. In order to achieve complete regression of tumors, CSCs have to be targeted. Recent advances in immunotherapies have shown promising outcomes in curing cancer, which are also applicable to target CSCs. CSCs express immune markers and exhibit specific immune characteristics in various cancers, which can be used in immunotherapies to target CSCs in the tumor microenvironment. Recently, various strategies have been used to target CSCs. Adaptive T-cells, dendritic cell (DC)-based vaccines, oncolytic viruses, immune checkpoint inhibitors, and combination therapies are now being used to target CSCs. Here, we discuss the feasibility of these immunological approaches and the recent trends in immunotherapies to target CSCs.

“…The majority of cells in bulk tumors have limited tumorigenic growth and self-renewal potential; indeed, only a small population of tumor cells possess a marked self-renewal capacity, and differentiation and the ability to generate new tumors [ 27 ]. These higher tumorigenic subpopulations are known as CSCs holding a higher tumorigenic potential [ 28 ]. The CSC concept has been proposed to explain the high degree of phenotypic and functional heterogeneity of cancer cells within a given tumor [ 21 ].…”

Section: Cancer Stem Cells: Implications For Hepatocarcinogenesismentioning

confidence: 99%

Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

Lee

Hong

2020

The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling pathways, such as aldehyde dehydrogenase (ALDH), CD133, epithelial cell adhesion molecule (EpCAM), Wnt/β-catenin signaling, and Notch signaling, contribute to the initiation and progression of various liver cancer types. Importantly, CSCs are markedly resistant to conventional therapeutic approaches and current targeted therapeutics. Therefore, it is believed that selectively targeting specific markers and/or signaling pathways of hepatic CSCs is an effective therapeutic strategy for treating chemotherapy-resistant liver cancer. Here, we provide an overview of the current knowledge on the hepatic CSC hypothesis and discuss the specific surface markers and critical signaling pathways involved in the development and maintenance of hepatic CSC subpopulations.