Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 7, 2020

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

Language: Английский

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Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 43(4), P. 678 - 719

Published: Nov. 6, 2021

Abstract Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing most common tumors in women worldwide. To date, no long-term or noninvasive treatment option exists for hormone-dependent uterine fibroids, due to limited knowledge about molecular mechanisms underlying initiation and development fibroids. This paper comprehensively summarizes recent research advances on focusing risk factors, origin, pathogenetic mechanisms, options. Additionally, we describe current interventions Finally, future perspectives studies summarized. Deeper mechanistic insights into tumor etiology complexity can contribute progress newer targeted therapies.

Language: Английский

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Mechanisms of cancer metastasis

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 87, P. 17 - 31

Published: Oct. 27, 2022

Metastatic cancer is almost always terminal, and more than 90% of deaths result from metastatic disease. Combating metastasis post-therapeutic recurrence successfully requires understanding each step progression. This review describes the current state knowledge etiology mechanism progression primary tumor growth to formation new tumors in other parts body. Open questions, avenues for future research, therapeutic approaches with potential prevent or inhibit through personalization patient's mutation and/or immune profile are also highlighted.

Language: Английский

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Role of p38 MAP kinase in cancer stem cells and metastasis

Oncogene, Journal Year: 2022, Volume and Issue: 41(23), P. 3177 - 3185

Published: April 30, 2022

Abstract Therapeutic resistance and metastatic progression are responsible for the majority of cancer mortalities. In particular, development is a significant barrier to efficacy treatments such as chemotherapy, radiotherapy, targeted therapies, immunotherapies. Cancer stem cells (CSCs) underlie treatment metastasis. p38 mitogen-activated protein kinase (p38 MAPK) downstream several CSC-specific signaling pathways, it plays an important role in CSC maintenance contributes metastasis chemoresistance. Therefore, therapeutic approaches targeting can sensitize tumors chemotherapy prevent progression.

Language: Английский

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Cancer-inducing niche: the force of chronic inflammation

British Journal of Cancer, Journal Year: 2022, Volume and Issue: 127(2), P. 193 - 201

Published: March 15, 2022

Language: Английский

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Nanog, as a key cancer stem cell marker in tumor progression

Gene, Journal Year: 2022, Volume and Issue: 827, P. 146448 - 146448

Published: March 22, 2022

Language: Английский

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Understanding the impact of feedback regulations on blood cell production and leukemia dynamics using model analysis and simulation of clinically relevant scenarios

Applied Mathematical Modelling, Journal Year: 2024, Volume and Issue: 129, P. 340 - 389

Published: Feb. 4, 2024

Acute myeloid leukemia (AML) is a paradigmatic example of stem cell-driven cancer. AML belongs to the most aggressive malignancies and has poor prognosis. A hallmark expansion malignant cells in bone marrow out-competition healthy blood-forming (hematopoietic) cells. In present study, we develop nonlinear ordinary differential equation model study impact feedback configurations kinetic cell properties such as symmetric self-renewal probability, differentiation asymmetric division proliferation rate, or death rate on leukemic population dynamics. The accounts for two types (mature immature) (cells that can divide have lost ability divide). considered here generalization previous models contains them special case. We consider multiple differ their self-renewal, differentiation, probabilities. Linearized stability analysis performed derive necessary sufficient conditions extinction our analysis, distinguish three steady states, namely purely states (presence absence cells), composite where coexist. Steady-state reveals under biologically plausible assumptions are unique. If exist, they non-unique form one-dimensional manifold. state locally asymptotically stable if only unstable. analytical results illustrated by numerical simulations. Our suggest slight increase probability decrease compared destabilization homeostatic equilibrium This finding line with arrest observed Changes these parameters opposite direction re-establish population. furthermore suggests configuration loops impacts regeneration, growth cells, burden late stage leukemias decline patients.

Language: Английский

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Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review

Cells, Journal Year: 2020, Volume and Issue: 9(8), P. 1896 - 1896

Published: Aug. 13, 2020

Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, recurrence metastasis. Drug resistance culminating relapse continues be associated with fatal disease. The stem cell theory posits that tumors are driven by specialized cells called (CSCs). CSCs a subpopulation of known resistant cause Whilst the debate on whether origins primary tumor rages on, have been further characterized many cancers data illustrating display abilities self-renew, resist enhanced epithelial mesenchymal (EMT) properties, expression ATP-binding cassette (ABC) membrane transporters, activation survival signaling pathways increased immune evasion as well DNA repair mechanisms. also heterogeneity consequential lack specific CSC markers presenting challenge their targeting. In this updated review we revisit within microenvironment (TME) present novel treatment strategies targeting CSCs. These promising include CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated epigenetic methods niche-microenvironmental factors differentiation. Lastly, recent clinical trials undertaken try turn tide against CSC-associated drug

Language: Английский

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Differences and similarities between cancer and somatic stem cells: therapeutic implications

Stem Cell Research & Therapy, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 18, 2020

Abstract Over the last decades, cancer survival rate has increased due to personalized therapies, discovery of targeted therapeutics and novel biological agents, application palliative treatments. Despite these advances, tumor resistance chemotherapy radiation rapid progression metastatic disease are still seen in many patients. Evidence shown that stem cells (CSCs), a sub-population share common characteristics with somatic (SSCs), contribute this therapeutic failure. The most critical properties CSCs their self-renewal ability capacity for differentiation into heterogeneous populations cells. Although only constitute low percentage total mass, can regrow mass on own. Initially identified leukemia, have subsequently been found cancers breast, colon, pancreas, brain. Common genetic phenotypic features both SSCs CSCs, including upregulated signaling pathways such as Notch, Wnt, Hedgehog, TGF-β. These play fundamental roles development well control cell fate relevant targeting CSCs. differences expression membrane proteins exosome-delivered microRNAs between also important specifically target cancer. Further research efforts should be directed toward elucidation improve existing therapies generate new clinically

Language: Английский

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C-myc Contributes to Malignancy of Lung Cancer: A Potential Anticancer Drug Target

Anticancer Research, Journal Year: 2020, Volume and Issue: 40(2), P. 609 - 618

Published: Feb. 1, 2020

Emerging evidence has provided important information on oncoproteins involved in cancer initiation, progression, metastasis, and resistance to current therapies. C-myc, one of the critical oncoproteins, been shown be implicated enhancing aggressiveness many cancers, mainly through its ability increase cell growth cellular survival mechanisms. Despite more precise earlier detection availability better therapies, lung remains most dreadful as it causes high mortality rate with relatively poor treatment success. In cancer, C-myc is frequently dysregulated associated unfavorable patient survival. plays a role regulation behaviors including growth, resistance, death, dissemination activation cycle driving proteins, an levels anti-apoptotic modulation metabolism. Besides, for stem (CSC) properties. Taken together, targeting well inhibiting could provide promising means resolving cancer. This review emphasizes molecular mechanism by which influences drug CSC maintenance, suggests target proteins that may benefit discovery design.

Language: Английский

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