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New Biomarkers and Therapy for Cancer Stem Cells
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New Biomarkers and Therapy for Cancer Stem Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 January 2025) | Viewed by 8592

Special Issue Editor

Prof. Dr. Pyung-Hwan Kim

E-Mail Website
Guest Editor
Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Republic of Korea
Interests: engineered stem cells

Special Issue Information

Dear Colleagues,

Cancer is still one of the most difficult diseases to treat despite the advancement of innovative medical technology, such as from first-generation chemotherapy to third-generation cancer immunotherapy. The recurrence of cancer is known to be caused by cancer stem cells. For complete cancer treatment, both cancer cells and cancer stem cells must induce death. However, cancer stem cells exist with very little population among cancer cells, and biomarkers to identify them have limitations in clinical application due to heterogeneity and plasticity between people. Therefore, a targeting strategy is needed along with the discovery of new biomarkers to treat cancer stem cells and diagnose and determine prognosis. This Special Issue addresses a wide range of topics linked with the research on biological functions according to the discovery of new biomarkers for cancer stem cells and new treatment strategies for an application study using them. Recent research and new advancements in this field and other related topics are welcome.

Prof. Dr. Pyung-Hwan Kim
Guest Editor

Manuscript Submission Information

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Keywords

  • biomarkers
  • cancer stem cells
  • targeted therapy

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Published Papers (4 papers)

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Research

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20 pages, 8016 KiB  
Article
Active Targeting of Versatile Nanocomplex Using the Novel Biomarker of Breast Cancer Stem Cells
by Eun-Young Koh, Keun-Sik Kim, Hee-Bin Park, Jong-Seok Kim and Pyung-Hwan Kim
Int. J. Mol. Sci. 2023, 24(1), 685; https://doi.org/10.3390/ijms24010685 - 30 Dec 2022
Cited by 6 | Viewed by 1943
Abstract
Breast cancer in women is one of the most common life-threatening malignancies. Despite of the development for the improved treatment, there are still many limitations to overcome. Among them, cancer stem cells (CSCs) are well known for tumor formation, development, cellular heterogeneity, and [...] Read more.
Breast cancer in women is one of the most common life-threatening malignancies. Despite of the development for the improved treatment, there are still many limitations to overcome. Among them, cancer stem cells (CSCs) are well known for tumor formation, development, cellular heterogeneity, and cancer recurrence. Therefore, to completely cure breast cancer, treatment of both cancer and CSC is required. To selectively target CSCs, we generated a liposome-based smart nano complex using CEACAM 6 (CD66c) antibody (Ab), a novel cell-surface biomarker of breast-derived CSCs (BCSCs) discovered in our previous research. Selective and increased cellular uptake was observed in BCSCs treated with CD66c Ab-conjugated rhodamine-labeled liposomes (CDRHOL) depending on the expression level of CD66c. CD66c Ab-conjugated doxorubicin (DOX)-loaded liposomes (CDDOXL) selectively showed increased cell killing effects in BCSCs with high CD66c expression levels. In an in vivo animal study, CDRHOL showed enhanced accumulation in xenografted BCSC tumors with low delivery into non-target organs. Moreover, mice treated with CDDOXL have assessed the decreased induction ability of immune response by low expression levels of pro-inflammatory cytokines and reduced liver toxicity by histopathological analysis. Finally, the improved antitumor effect of CDDOXL was evaluated in a metastatic BCSC mouse model via systemic administration. Collectively, our study is the first to demonstrate that a multi-functional nano complex using a novel surface biomarker of BCSC may be a more effective therapeutic agent for the treatment of cancer and CSCs. Full article
(This article belongs to the Special Issue New Biomarkers and Therapy for Cancer Stem Cells)
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Review

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11 pages, 235 KiB  
Review
Natural Bioactive Agents: Testable Stem Cell-Targeting Alternatives for Therapy-Resistant Breast Cancer
by Nitin T. Telang
Int. J. Mol. Sci. 2025, 26(6), 2529; https://doi.org/10.3390/ijms26062529 - 12 Mar 2025
Viewed by 568
Abstract
Long-term treatment options for conventional chemo-endocrine therapy and molecular-pathway-based targeted therapy are associated with acquired therapy resistance and the emergence of drug-resistant cancer-initiating stem cell populations, leading to the progression of metastatic disease. These treatment options are based on the expression status of [...] Read more.
Long-term treatment options for conventional chemo-endocrine therapy and molecular-pathway-based targeted therapy are associated with acquired therapy resistance and the emergence of drug-resistant cancer-initiating stem cell populations, leading to the progression of metastatic disease. These treatment options are based on the expression status of estrogen receptor-α (ER-α), progesterone receptor (PR) hormone receptors, and/or of human epidermal growth factor receptor-2 (HER-2). The breast cancer subtypes Luminal A, Luminal B, and HER-2-enriched express hormone/growth factor receptors and exhibit a favorable response to hormone receptor modulators and growth factor receptor antagonists. The triple-negative breast cancer subtype lacks the expression of hormone/growth factor receptors and responds only to cytotoxic conventional chemotherapy. The clinical limitations, due to the modest therapeutic responses of chemo-resistant cancer-initiating stem cells, emphasize the need for the identification of stem cells targeting testable alternatives for therapy-resistant breast cancer. Developed drug-resistant stem cell models exhibit upregulated expression of select cellular biomarker tumor spheroid (TS) formations and cluster of differentiation44 (CD44), DNA-binding protein (NANOG), and octamer-binding protein-4 (OCT-4) molecular biomarkers that represent novel experimentally modifiable quantitative endpoints. Naturally occurring dietary phytochemicals and nutritional herbs containing polyphenols, flavones, terpenes, saponins, lignans, and tannins have documented human consumption, lack systemic toxicity, lack phenotypic drug resistance, and exhibit preclinical efficacy. Constituent bioactive agents may provide testable stem cell-targeting alternatives. The present report provides an overview of (i) clinically relevant cellular models and drug-resistant cancer stem cell models for breast cancer subtypes, (ii) evidence for preclinical efficacy and mechanistic leads for natural phytochemicals and nutritional herbs, and (iii) the potential for the stem cell-targeting efficacy of natural bioactive agents as testable drug candidates for therapy-resistant breast cancer. Full article
(This article belongs to the Special Issue New Biomarkers and Therapy for Cancer Stem Cells)
43 pages, 1604 KiB  
Review
Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches
by Ivan Lučić, Matea Kurtović, Monika Mlinarić, Nikolina Piteša, Ana Čipak Gašparović, Maja Sabol and Lidija Milković
Int. J. Mol. Sci. 2023, 24(13), 10683; https://doi.org/10.3390/ijms241310683 - 26 Jun 2023
Cited by 3 | Viewed by 2525
Abstract
Breast cancer (BC) and ovarian cancer (OC) are among the most common and deadly cancers affecting women worldwide. Both are complex diseases with marked heterogeneity. Despite the induction of screening programs that increase the frequency of earlier diagnosis of BC, at a stage [...] Read more.
Breast cancer (BC) and ovarian cancer (OC) are among the most common and deadly cancers affecting women worldwide. Both are complex diseases with marked heterogeneity. Despite the induction of screening programs that increase the frequency of earlier diagnosis of BC, at a stage when the cancer is more likely to respond to therapy, which does not exist for OC, more than 50% of both cancers are diagnosed at an advanced stage. Initial therapy can put the cancer into remission. However, recurrences occur frequently in both BC and OC, which are highly cancer-subtype dependent. Therapy resistance is mainly attributed to a rare subpopulation of cells, named cancer stem cells (CSC) or tumor-initiating cells, as they are capable of self-renewal, tumor initiation, and regrowth of tumor bulk. In this review, we will discuss the distinctive markers and signaling pathways that characterize CSC, their interactions with the tumor microenvironment, and the strategies they employ to evade immune surveillance. Our focus will be on identifying the common features of breast cancer stem cells (BCSC) and ovarian cancer stem cells (OCSC) and suggesting potential therapeutic approaches. Full article
(This article belongs to the Special Issue New Biomarkers and Therapy for Cancer Stem Cells)
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14 pages, 1169 KiB  
Review
Protein Posttranslational Modification in Stemness Remodeling and Its Emerging Role as a Novel Therapeutic Target in Gastrointestinal Cancers
by Yifei Wang and Man Tong
Int. J. Mol. Sci. 2023, 24(11), 9173; https://doi.org/10.3390/ijms24119173 - 24 May 2023
Cited by 5 | Viewed by 2651
Abstract
The posttranslational modifications (PTMs) of proteins, as critical mechanisms for protein regulation, are well known to enhance the functional diversity of the proteome and dramatically participate in complicated biological processes. Recent efforts in the field of cancer biology have illustrated the extensive landscape [...] Read more.
The posttranslational modifications (PTMs) of proteins, as critical mechanisms for protein regulation, are well known to enhance the functional diversity of the proteome and dramatically participate in complicated biological processes. Recent efforts in the field of cancer biology have illustrated the extensive landscape of PTMs and their crosstalk with a wide range of pro-tumorigenic signaling pathways that decisively contribute to neoplastic transformation, tumor recurrence, and resistance to oncotherapy. Cancer stemness is an emerging concept that maintains the ability of tumor cells to self-renew and differentiate and has been recognized as the root of cancer development and therapy resistance. In recent years, the PTM profile for modulating the stemness of various tumor types has been identified. This breakthrough has shed light on the underlying mechanisms by which protein PTMs maintain cancer stemness, initiate tumor relapse, and confer resistance to oncotherapies. This review focuses on the latest knowledge of protein PTMs in reprogramming the stemness of gastrointestinal (GI) cancer. A deeper understanding of abnormal PTMs in specific proteins or signaling pathways provides an opportunity to specifically target cancer stem cells and highlights the clinical relevance of PTMs as potential biomarkers and therapeutic targets for patients with GI malignancies. Full article
(This article belongs to the Special Issue New Biomarkers and Therapy for Cancer Stem Cells)
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