Overview of Cancer Stem Cells and Stemness for Community Oncologists

Abstract

Advances in cancer research in the past have led to an evolving understanding of cancer pathogenesis and the development of novel drugs that significantly improve patient outcomes. However, many patients still encounter treatment resistance, recurrence, or metastasis and eventually die from progressing disease. Experimental evidence indicates that a subpopulation of cancer cells, called cancer stem cells (CSCs), possess “stemness” properties similar to normal stem cells, including self-renewal, differentiation, and proliferative potential. These stemness properties are lost during differentiation and are governed by pathways such as STAT3, NANOG, NOTCH, WNT, and HEDGEHOG, which are highly dysregulated in CSCs due to genetic and epigenetic changes. Promising results have been observed in preclinical models targeting these CSCs through the disruption of stemness pathways in combination with current treatment modalities. This has led to anti-CSC–based clinical trials in multiple stages of development. In this review, we discuss the role of CSCs and stemness pathways in cancer treatment and how they relate to clinical observations. Because CSCs and the stemness pathways governing them may explain the negative clinical outcomes observed during treatment, it is important for oncologists to understand how they contribute to cancer progression and how they may be targeted to improve patient outcomes.

Knockdown of XB130 restrains cancer stem cell‐like phenotype through inhibition of Wnt/β‐Catenin signaling in breast cancer

“…Some studies have also suggested that breast cancer cells could acquire the mesenchymal‐like phenotype via EMT, which leads to an increase in the number of stem cells with self‐renewal and spheroidizing ability . Additionally, a part of cancer cells develops the ability of invasion and metastasis through EMT when leaving the primary tumor, while establishes the critical self‐renewal ability as cancer stem cell . As shown by our results, compared with the shNT control cells, knockdown of XB130 inhibited the spheroidizing ability of stem cells and decreased the proportion of SP + cells in vitro.…”

Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities

“…These observations have stimulated the development of anti-CSC therapeutic strategies (Gupta et al 2009b) often targeting surface markers and/or signaling pathways that are aberrantly activated and contribute to CSC proliferation and/or survival. Some of these therapeutic modalities are currently being tested in preclinical and clinical studies (Chen et al 2013;Lathia and Liu 2017).…”

MEIS1 knockdown may promote differentiation of esophageal squamous carcinoma cell line KYSE‐30

“…CSCs preserve self-renewal and proliferative potential via inhibiting differentiation signaling pathways during cancer initiation and development (Jin, Jin, & Kim, 2017;Lathia & Liu, 2017). Remarkably, the balance between differentiation and self-renewal capabilities of CSCs produces the bulk of heterogeneous tumor mass contributing in aggressive and stemness phenotypes (Lathia & Liu, 2017). Specific gene expression profiles are needed for tumor cell differentiation which are dictated through different signaling pathways, transcription factor activities, as well as epigenetic alterations such as DNA modifications (Jögi, Vaapil, Johansson, & Påhlman, 2012).…”