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Results for “Cancer stemness”

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PubMed2006

Profiling cancer stem cells using protein array technology.

Since cancer cells and somatic stem cells share the biological characteristics of self-renewal and proliferation, it has been suggested that the principles of stem cell biology can be applied to improve our understanding of cancer biology. Recent studies have shown that the majority of cancers appear to originate from a small subset of cells that have the ability of self-renewal and to proliferate, namely 'cancer stem cells'. The isolation of cancer stem cells has been demonstrated using cell surface markers in haematopoietic and non-haematopoietic malignancies. Advances in protein array technologies have enabled the use of minuscule amounts of biological materials to profile these cells at the molecular level. Using a combination of protein arrays and cancer stem cell isolation techniques, a higher resolution molecular profiling can be performed, which might improve therapies targeting the cancer stem cells.

Cell Communication↗

PubMed2006

Cancer stem cells: redefining the paradigm of cancer treatment strategies.

Cancer has been known to arise from long-lived cells in the body and to possess properties in common with undifferentiated, embryonic cells. Recent findings of a population of cells in solid tumors resembling stem cells supports a stem cell model of cancer. A scheme in which all cancers initiate from "activated' stem cells helps bring together data from genetic, cell biology, and epidemiology studies. Cancer can arise from embryonic cells in the case of childhood tumors; hormone-activated stem cells in the case of breast cancer; and following chronic activation of stem cells caused by tissue damage. This scheme helps explain the failure of many cancer therapies, points out deficiencies in certain research approaches, and focuses the problem on a subset of cells that can be explicitly targeted, leading to more efficient therapy.

Animals↗

PubMed2006

[Progress of cancer stem cells of solid tumor].

Stem cells have some characteristics similar to tumor cells, and may be the origin of tumor cells. Stem cell-like subpopulation has been isolated and identified from hematopoietic system malignancies and solid tumors, and defined as cancer stem cells. Cancer stem cells play important roles in the initiation and progression of malignancies. Tumor might be a kind of diseases of stem cells, and this finding may help to understand the mechanisms of tumorigenesis and instruct clinical therapeutics.

AC133 Antigen↗

PubMed2026

Targeting cancer stem cells predicts response and reverses chemoresistance in ascites-derived ovarian cancer organoids.

BACKGROUND: Ovarian cancer (OC) is frequently diagnosed at an advanced stage, where tumor heterogeneity and rapid development of chemoresistance contribute to a poor prognosis. The lack of reliable predictive biomarkers further hinders the development of effective treatment strategies. Patient-derived organoids (PDOs) have recently emerged as promising preclinical models with the potential to predict therapeutic responses. METHODS: OC PDOs were generated from ascites samples representing diverse histological subtypes. Histological and genomic fidelity to parental tumors was confirmed through histopathological analysis and whole-exome sequencing. Drug sensitivity to cisplatin and poly (ADP-ribose) polymerase (PARP) inhibitors was evaluated and correlated with 1-year clinical outcomes. We also investigated the therapeutic efficacy of oncolytic herpes simplex virus 2 (OH2) both as a single agent and in combination with cisplatin. The expression of cancer stem cell (CSC) markers CD44 and ALDH1A1 under treatment conditions was analyzed using immunohistochemistry and flow cytometry. RESULTS: PDOs were successfully established with an 86.2% success rate. These PDOs faithfully recapitulated the histopathological and genomic features of their corresponding tumors, maintaining intratumoral heterogeneity, and were amenable to xenotransplantation. Drug sensitivity assays demonstrated that PDOs accurately predicted patient-specific responses to cisplatin and PARP inhibitors. OH2 exhibited direct cytotoxicity in both cisplatin-sensitive and cisplatin-resistant PDOs, reducing cell viability by 20-60%. Notably, the combination treatment with OH2 and cisplatin enhanced antitumor efficacy, resulting in a significant reduction of the CD44+CSC subpopulation. CONCLUSIONS: Ascites-derived OC PDOs represent a robust platform for individualized drug testing. The combination of OH2 and cisplatin offers a novel and effective strategy for circumventing chemoresistance in OC.

Female↗

PubMed2005

Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis.

The failure to eradicate cancer may be as fundamental as a misidentification of the target. Current therapies succeed at eliminating bulky disease but often miss a tumor reservoir that is the source of disease recurrence and metastasis. Recent advances in the understanding of tissue development and repair cause us to revisit the process of drug resistance as it applies to oncogenesis and tumor heterogeneity. The cancer stem cell hypothesis states that the cancer-initiating cell is a transformed tissue stem cell, which retains the essential property of self-protection through the activity of multiple drug resistance (MDR) transporters. This resting constitutively drug-resistant cell remains at low frequency among a heterogeneous tumor mass. In the context of this hypothesis, the authors review the discovery of MDR transporters in cancer and normal stem cells and the failure of MDR reversal agents to increase the therapeutic index of substrate antineoplastic agents.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2005

Is cancer stem cell a cell, or a multicellular unit capable of inducing angiogenesis?

Cancer stem cells are presently viewed as carriers of the growth initiating potential, repopulation capability and drug resistance in tumors. However, many of these fundamental properties of cancer are host-related, modified by cell-cell interactions and/or dependent on angiogenesis. Indeed, it is well established that co-injection of cancer cells with their irradiated (mitotically dead) counterparts, or with Matrigel can significantly increase their tumor forming capacity (i.e. the attribute presently associated with cancer cell 'stemness'). Similarly transfection of angiogenic factors (e.g., VEGF/VPF) can promote such capacity in certain cell lines. Moreover, injection site (e.g., orthotopic vs. ectopic) may significantly modulate tumor take in experimental settings. These observations cannot be reconciled with the paradigm that tumor initiation potential is a fixed, constitutive and cell autonomous feature of a subset of cancer cells expressing stem cell markers (e.g., CD133, Sca1 and other). Instead, it is proposed here that 'stemness' in cancer (perhaps unlike in normal self renewing tissues), rather then being assigned to a particular readily identifiable cell subset, could be a property of interactive clusters of cancer cells (perhaps including, but not limited to cells with stem cell markers). Such 'multicellular units' would become equipped with properties experimentally perceived as 'stemness', i.e. the capacity to initiate tumor growth, when they express the capacity to induce angiogenesis. It is also postulated here that, while the pursuit of subsets of cancer cells harbouring stem cell markers has been fascinating and revealing, due to aforementioned limitations of the present stem cell concept and presumed intractability (e.g., mutability) of such cells, further therapeutic promise may reside in a better definition of 'multicellular angiogenic cancer stem units'.

AC133 Antigen↗

PubMed2006

Delivering cancer stem cell therapies - a role for nanomedicines?

Cancer stem cells (CSCs), i.e. cancer cells that can self-renew, constitute only a minority of the cells of a tumour, but, because of their ability to initiate and repopulate tumours, failure to control CSCs can potentially lead to tumour re-growth, even though the bulk tumour may have been treated successfully. Nanomedicines improve spatio-temporal control over drug kinetics and distribution, thus opening the prospect of safer and more specific therapies to address the challenges posed by CSCs. In particular, these systems have the potential to facilitate CSC-aware therapy by overcoming resistance to conventional cytotoxic drugs and by targeting novel therapies to the tumour and CSC-marker positive cells. This review examines the implications of the CSC paradigm specifically for the development of nanomedicines, i.e. therapies based on macromolecules or supramolecular aggregates.

Antineoplastic Agents↗

PubMed2026

Rewiring Cellular Context as A Central Mechanism Governing Cancer Stem Cell Survival: Insights from ESC Comparisons.

Cancer stem cells (CSCs) drive tumor initiation, metastasis, and therapy resistance, yet their remarkable persistence remains poorly understood. While CSCs share stemness attributes with embryonic stem cells (ESCs), including self-renewal, transcriptional plasticity, and permissive chromatin, they exhibit a fundamentally divergent regulatory logic that prioritizes survival over developmental fidelity. ESCs maintain globally open chromatin that supports transcriptional hyperactivity but predisposes them to apoptosis under genotoxic stress, whereas CSCs maintain dynamically inducible, permissive chromatin at survival loci while repressing differentiation programs, enabling adaptive stress responses. We advance the hypothesis that CSC persistence emerges not from any single factor, but from the integrative rewiring of signaling cascades (Wnt/β-catenin, Notch, Hedgehog, PI3K/AKT/mTOR), stress-responsive transcription factors (HIFs, NF-κB, STAT3), and core pluripotency networks (OCT4, SOX2, NANOG) within a survival-centric context, reinforced by dynamic chromatin remodeling, inducible super-enhancer landscapes, and microenvironmental cues (hypoxia, inflammation, matrix stiffness). Within this framework, the E2F family serves as a key contextual integrator: in ESCs, constitutive E2F activity triggers p53-mediated apoptosis upon DNA damage, preserving genomic integrity; in CSCs, deregulated E2F activity redirects transcription toward DNA repair, antioxidant defenses, and anti-apoptotic programs. This functional divergence underscores that phenotypic outcome is determined by the broader cellular and epigenetic landscape rather than any single factor. We conclude that CSC persistence is an emergent property of this integrated, survival-centric program, fundamentally distinct from the developmental imperative of ESCs. Effective therapeutic strategies must therefore move beyond targeting individual pathways to dismantle the interconnected regulatory networks that define the CSC survival context, offering a more robust approach to overcome therapy resistance and prevent tumor relapse.

Cancer Stem Cells (CSCs)↗

PubMed2005

Opinion: the origin of the cancer stem cell: current controversies and new insights.

Most tumours are derived from a single cell that is transformed into a cancer-initiating cell (cancer stem cell) that has the capacity to proliferate and form tumours in vivo. However, the origin of the cancer stem cell remains elusive. Interestingly, during development and tissue repair the fusion of genetic and cytoplasmic material between cells of different origins is an important physiological process. Such cell fusion and horizontal gene-transfer events have also been linked to several fundamental features of cancer and could be important in the development of the cancer stem cell.

Animals↗

PubMed2005

Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells.

Long-term cultures of telomerase-transduced adult human mesenchymal stem cells (hMSC) may evolve spontaneous genetic changes leading to tumorigenicity in immunodeficient mice (e.g., hMSC-TERT20). We wished to clarify whether this unusual phenotype reflected a rare but dominant subpopulation or if the stem cell origin allowed most cells to behave as cancer stem cells. Cultures of the hMSC-TERT20 strain at population doubling 440 were highly clonogenic (94%). From 110 single-cell clones expanded by 20 population doublings, 6 underwent detailed comparison. Like the parental population, each clone had approximately 1.2 days doubling time with loss of contact inhibition. All retained 1,25-(OH)(2) vitamin D(3)-induced expression of osteoblastic markers: collagen type I, alkaline phosphatase, and osteocalcin. All shared INK4a/ARF gene locus deletion and epigenetic silencing of the DBCCR1 tumor suppressor gene. Despite in vitro commonality, only four of six clones shared the growth kinetics and 100% tumorigenicity of the parental population. In contrast, one clone consistently formed latent tumors and the other established tumors with only 30% penetrance. Changing the in vitro microenvironment to mimic in vivo growth aspects revealed concordant clonal heterogeneity. Latent tumor growth correlated with extracellular matrix entrapment of multicellular spheroids and high procollagen type III expression. Poor tumorigenicity correlated with in vitro serum dependence and high p27(Kip1) expression. Aggressive tumorigenicity correlated with good viability plus capillary morphogenesis on serum starvation and high cyclin D1 expression. Thus, hMSC-TERT20 clones represent cancer stem cells with hierarchical tumorigenicity, providing new models to explore the stem cell hypothesis for cancer.

Adult↗

PubMed2007

Beyond tumorigenesis: cancer stem cells in metastasis.

The importance of cancer stem cells (CSCs) in tumor-initiation has been firmly established in leukemia and recently reported for a variety of solid tumors. However, the role of CSCs in multistage cancer progression, particularly with respect to metastasis, has not been well-defined. Cancer metastasis requires the seeding and successful colonization of specialized CSCs at distant organs. The biology of normal stem cells and CSCs share remarkable similarities and may have important implications when applied to the study of cancer metastasis. Furthermore, overlapping sets of molecules and pathways have recently been identified to regulate both stem cell migration and cancer metastasis. These molecules constitute a complex network of cellular interactions that facilitate both the initiation of the pre-metastasis niche by the primary tumor and the formation of a nurturing organ microenvironment for migrating CSCs. In this review, we surveyed the recent advances in this dynamic field and propose a unified model of cancer progression in which CSCs assume a central role in both tumorigenesis and metastasis. Better understanding of CSCs as a fundamental component of the metastatic cascade will lead to novel therapeutic strategies against metastatic cancer.

Animals↗

PubMed2006

Breast cancer stem cells: an overview.

The theory that cancer may be originated and sustained by a small proportion of stem-like, self-renewing cells (termed 'cancer stem cells') has gained support in recent years. Breast cancer stem cells have been identified as CD44+CD24- breast tumour cells and have recently been isolated and propagated in vitro. It has been demonstrated that these cells exclusively retain the ability to form new tumours in mouse models and that they display stem/progenitor cell properties. The ability to identify breast cancer stem cells in vivo and to propagate them in vitro provides the means to compare them with normal cells, in order to investigate from which cell they originate, which molecular alterations critically affect them, and how they interact with the microenvironment. Elucidation of these critical points is essential to develop new therapeutic strategies and to improve diagnosis and prognosis for breast cancer patients.

Breast Neoplasms↗

PubMed2006

Successful therapy must eradicate cancer stem cells.

Despite significant improvements in cancer therapy, tumor recurrence is frequent and can be due to a variety of mechanisms, including the evolution of resistance and tumor progression. Cancer stem cells have been postulated to maintain tumor growth similar to normal stem cells maintaining tissue homeostasis. Recently, the existence of these malignant stem cells has been proven for hematological as well as some solid tumors. Tumor stem cells are not targeted by standard therapy and might be responsible for treatment failure and tumor recurrence in many patients. We designed a simple mathematical model to demonstrate the importance of eliminating tumor stem cells. We explored different therapeutic scenarios to illustrate the properties required from novel therapeutic agents for successful tumor treatment. We show that successful therapy must eradicate tumor stem cells.

Animals↗

PubMed2005

Prospective identification of tumorigenic prostate cancer stem cells.

Existing therapies for prostate cancer eradicates the bulk of cells within a tumor. However, most patients go on to develop androgen-independent disease that remains incurable by current treatment strategies. There is now increasing evidence in some malignancies that the tumor cells are organized as a hierarchy originating from rare stem cells that are responsible for maintaining the tumor. We report here the identification and characterization of a cancer stem cell population from human prostate tumors, which possess a significant capacity for self-renewal. These cells are also able to regenerate the phenotypically mixed populations of nonclonogenic cells, which express differentiated cell products, such as androgen receptor and prostatic acid phosphatase. The cancer stem cells have a CD44+/alpha2beta1hi/CD133+ phenotype, and we have exploited these markers to isolate cells from a series of prostate tumors with differing Gleason grade and metastatic states. Approximately 0.1% of cells in any tumor expressed this phenotype, and there was no correlation between the number of CD44+/alpha2beta1hi/CD133+ cells and tumor grade. The identification of a prostate cancer stem cell provides a powerful tool to investigate the tumorigenic process and to develop therapies targeted to the stem cell.

AC133 Antigen↗

PubMed2026

Engineering CRISPR nanoplatforms to deplete cancer stem cells: Delivery checkpoints, target plasticity, and clinical viability.

Cancer stem cells (CSCs) sustain tumor initiation, therapy resistance, and relapse, yet evade durable control because they switch phenotype, enter quiescence, shelter within protective niches, resist drug efflux, and share markers with normal stem cells. Programmable CRISPR editing can disable intracellular self-renewal dependencies that antibodies and small molecules cannot reach, whereas only nanoscale carriers can confine such editing to intended cells; neither component alone solves the CSC problem. This review reframes CSC-directed CRISPR nanomedicine as an integrated design problem. We examine why target plasticity defeats static single-marker targeting; the sequential delivery checkpoints spanning blood stability, organ selection, tumor penetration, CSC recognition, endosomal escape, and productive editing; and advanced architectures including organ-selective lipid nanoparticles, biomimetic and vesicle carriers, metal-organic frameworks, and logic-gated systems. Genotoxicity, immunogenicity, incomplete depletion, manufacturing reproducibility, and absent CSC-specific clinical evidence remain limiting. Clinical viability, not imminent cure, is the realistic near-term objective.

Neoplastic Stem Cells↗

PubMed2007

Cancer stem cells and oncology therapeutics.

PURPOSE OF REVIEW: An overview of the latest developments in the cancer stem cells field and their potential use in the oncology drug discovery process. RECENT FINDINGS: Recent studies provided evidence of the existence of a subpopulation of cells within a variety of tumor types with a tumorigenic potential that is lacking in the rest of the cells within these tumors. There is mounting evidence that such cells exist in almost all tumor types. Work on the characterization of these cells suggests that deregulation of pathways responsible for stem cell self-renewal is a likely requirement for carcinogenesis and targeting such pathways might be curative. Progress has been made to develop more relevant in-vitro and in-vivo models that incorporate these findings. SUMMARY: Cancer stem cells have been identified in a variety of tumors. Characterization of these cells, determining how they originate and developing relevant assays is a work in progress. Incorporating these findings in the cancer drug discovery process might lead to better therapeutics.

Animals↗

PubMed2006

Cancer stem cells: an old idea--a paradigm shift.

Although the concept that cancers arise from "stem cells" or "germ cells" was first proposed about 150 years ago, it is only recently that advances in stem cell biology have given new impetus to the "cancer stem cell hypothesis." Two important related concepts of this hypothesis are that (a) tumors originate in either tissue stem cells or their immediate progeny through dysregulation of the normally tightly regulated process of self-renewal. As a result of this, (b) tumors contain a cellular subcomponent that retains key stem cell properties. These properties include self-renewal, which drives tumorigenesis, and differentiation albeit aberrant that contributes to cellular heterogeneity. Recent experimental evidence in a variety of tumors has lent strong support to the cancer stem cell hypothesis that represents a paradigm shift in our understanding of carcinogenesis and tumor cell biology. This hypothesis has fundamental implications for cancer risk assessment, early detection, prognostication, and prevention. Furthermore, the current development of cancer therapeutics based on tumor regression may have produced agents that kill differentiated tumor cells while sparing the rare cancer stem cell population. The development of more effective cancer therapies may thus require targeting this important cell population.

Animals↗

PubMed2006

The cancer stem cell hypothesis: a work in progress.

There is a growing body of evidence that supports the idea that malignant tumors are initiated and maintained by a population of tumor cells that share similar biologic properties to normal adult stem cells. This model, the cancer stem cell (CSC) hypothesis, is based on the observation that tumors, like adult tissues, arise from cells that exhibit the ability to self-renew as well as give rise to differentiated tissue cells. Although the concept of the CSC is not entirely new, advances made over the past two decades in our understanding of normal stem cell biology in conjunction with the recent application of these concepts to experimentally define CSCs have resulted in the identification of CSCs in several human malignancies.

Adult Stem Cells↗