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The Implications and Future Perspectives of Nanomedicine for Cancer Stem Cell Targeted Therapies.

ABSTRACT: Cancer stem cells (CSCs) are believed to exhibit distinctive self-renewal, proliferation, and differentiation capabilities, and thus play a significant role in various aspects of cancer. CSCs have significant impacts on the progression of tumors, drug resistance, recurrence and metastasis in different types of malignancies. Due to their primary role, most researchers have focused on developing anti-CSC therapeutic strategies, and tremendous efforts have been put to explore methods for selective eradication of these therapeutically resistant CSCs. In recent years, many reports have shown the use of CSCs-specific approaches such as ATP-binding cassette (ABC) transporters, blockade of self-renewal and survival of CSCs, CSCs surface markers targeted drugs delivery and eradication of the tumor microenvironment. Also, various therapeutic agents such as small molecule drugs, nucleic acids, and antibodies are said to destroy CSCs selectively. Targeted drug delivery holds the key to the success of most of the anti-CSCs based drugs/therapies. The convention CSCs-specific therapeutic agents, suffer from various problems. For instance, limited water solubility, small circulation time and inconsistent stability of conventional therapeutic agents have significantly limited their efficacy. Recent advancement in the drug delivery technology has demonstrated that specially designed nanocarrier-based drug delivery approaches (nanomedicine) can be useful in delivering sufficient amount of drug molecules even in the most interiors of CSCs niches and thus can overcome the limitations associated with the conventional free drug delivery methods. The nanomedicine has also been promising in designing effective therapeutic regime against pump-mediated drug resistance (ATP-driven) and reduces detrimental effects on normal stem cells. Here we focus on the biological processes regulating CSCs' drug resistance and various strategies developed so far to deal with them. We also review the various nanomedicine approaches developed so far to overcome these CSCs related issues and their future perspectives.

SUBMITTER: Singh VK

PROVIDER: S-EPMC5520001 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, the analysis of biomarkers in cancer patients within the pre- and post-therapeutic period is required to identify several types of cells, which carry a risk for a disease progression and subsequent post-therapeutic relapse. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. At the time point of tumor initiation, CSCs originate from either differentiated cells or adult tissue resident stem cells. Due to their importance, several biomarkers that characterize CSCs have been identified and correlated to diagnosis, therapy and prognosis. However, CSCs have been shown to display a high plasticity, which changes their phenotypic and functional appearance. Such changes are induced by chemo- and radiotherapeutics as well as senescent tumor cells, which cause alterations in the tumor microenvironment. Induction of senescence causes tumor shrinkage by modulating an anti-tumorigenic environment in which tumor cells undergo growth arrest and immune cells are attracted. Besides these positive effects after therapy, senescence can also have negative effects displayed post-therapeutically. These unfavorable effects can directly promote cancer stemness by increasing CSC plasticity phenotypes, by activating stemness pathways in non-CSCs, as well as by promoting senescence escape and subsequent activation of stemness pathways. At the end, all these effects can lead to tumor relapse and metastasis. This review provides an overview of the most frequently used CSC markers and their implementation as biomarkers by focussing on deadliest solid (lung, stomach, liver, breast and colorectal cancers) and hematological (acute myeloid leukemia, chronic myeloid leukemia) cancers. Furthermore, it gives examples on how the CSC markers might be influenced by therapeutics, such as chemo- and radiotherapy, and the tumor microenvironment. It points out, that it is crucial to identify and monitor residual CSCs, senescent tumor cells, and the pro-tumorigenic senescence-associated secretory phenotype in a therapy follow-up using specific biomarkers. As a future perspective, a targeted immune-mediated strategy using chimeric antigen receptor based approaches for the removal of remaining chemotherapy-resistant cells as well as CSCs in a personalized therapeutic approach are discussed.

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The Implications and Future Perspectives of Nanomedicine for Cancer Stem Cell Targeted Therapies.

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