scholarly journals Microenvironmental variables need to effect intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity

2013 ◽  
Author(s):  
Jacob G Scott ◽  
Prakash Chinnaiyan ◽  
Alexander ARA Anderson ◽  
Anita Hjelmeland ◽  
David Basanta
Keyword(s):  
Stem Cell ◽  
Therapeutic Strategy ◽  
Tissue Growth ◽  
Genetic Mutations ◽  
Phenotypic Traits ◽  
Cell Behaviour ◽  
New Information ◽  
Cancer Initiation ◽  
Cancer Types ◽  
Direct Feedback

Since the discovery of tumour initiating cells (TICs) in solid tumours, studies focussing on their role in cancer initiation and progression have abounded. The biological interrogation of these cells continues to yield volumes of information on their pro-tumourigenic behaviour, but actionable generalised conclusions have been scarce. Further, new information suggesting a dependence of tumour composition and growth on the microenvironment has yet to be studied theoretically. To address this point, we created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue with a simple microenvironment. Using the model we explored the phenotypic traits inherent to the tumour initiating cells and the effect of the microenvironment on tissue growth. We identify the regions in phenotype parameter space where TICs are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour maintenance. As our parameters and model are non- specific, they could apply to any tissue TIC and do not assume specific genetic mutations. Targeting these phenotypic traits could represent a generalizable therapeutic strategy across cancer types. Further, we find that the microenvironmental variable does not strongly effect the outcomes, suggesting a need for direct feedback from the microenvironment onto stem-cell behaviour in future modelling endeavours.

scholarly journals Microenvironmental variables need to effect intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity

2013 ◽  
Author(s):  
Jacob G Scott ◽  
Prakash Chinnaiyan ◽  
Alexander ARA Anderson ◽  
Anita Hjelmeland ◽  
David Basanta
Keyword(s):  
Stem Cell ◽  
Therapeutic Strategy ◽  
Tissue Growth ◽  
Genetic Mutations ◽  
Phenotypic Traits ◽  
Cell Behaviour ◽  
New Information ◽  
Cancer Initiation ◽  
Cancer Types ◽  
Direct Feedback

Since the discovery of tumour initiating cells (TICs) in solid tumours, studies focussing on their role in cancer initiation and progression have abounded. The biological interrogation of these cells continues to yield volumes of information on their pro-tumourigenic behaviour, but actionable generalised conclusions have been scarce. Further, new information suggesting a dependence of tumour composition and growth on the microenvironment has yet to be studied theoretically. To address this point, we created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue with a simple microenvironment. Using the model we explored the phenotypic traits inherent to the tumour initiating cells and the effect of the microenvironment on tissue growth. We identify the regions in phenotype parameter space where TICs are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour maintenance. As our parameters and model are non- specific, they could apply to any tissue TIC and do not assume specific genetic mutations. Targeting these phenotypic traits could represent a generalizable therapeutic strategy across cancer types. Further, we find that the microenvironmental variable does not strongly effect the outcomes, suggesting a need for direct feedback from the microenvironment onto stem-cell behaviour in future modelling endeavours.

scholarly journals Microenvironmental variables must influence intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity

2013 ◽  
Author(s):  
Jacob Scott ◽  
Anita Hjelmeland ◽  
Prakash Chinnaiyan ◽  
Alexander R A Anderson ◽  
David Basanta
Keyword(s):  
Stem Cell ◽  
Therapeutic Strategy ◽  
Tissue Growth ◽  
Genetic Mutations ◽  
Phenotypic Traits ◽  
Cell Behaviour ◽  
New Information ◽  
Cancer Initiation ◽  
Cancer Types ◽  
Direct Feedback

Since the discovery of tumour initiating cells (TICs) in solid tumours, studies focussing on their role in cancer initiation and progression have abounded. The biological interrogation of these cells continues to yield volumes of information on their pro-tumourigenic behaviour, but actionable generalised conclusions have been scarce. Further, new information suggesting a dependence of tumour composition and growth on the microenvironment has yet to be studied theoretically. To address this point, we created a hybrid, discrete/continuous computational cellular automaton model of a generalised stem-cell driven tissue with a simple microenvironment. Using the model we explored the phenotypic traits inherent to the tumour initiating cells and the effect of the microenvironment on tissue growth. We identify the regions in phenotype parameter space where TICs are able to cause a disruption in homeostasis, leading to tissue overgrowth and tumour maintenance. As our parameters and model are non-specific, they could apply to any tissue TIC and do not assume specific genetic mutations. Targeting these phenotypic traits could represent a generalizable therapeutic strategy across cancer types. Further, we find that the microenvironmental variable does not strongly effect the outcomes, suggesting a need for direct feedback from the microenvironment onto stem-cell behaviour in future modelling endeavours.

scholarly journals Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2746
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cell ◽  
Liver Cancer ◽  
Signaling Pathways ◽  
Therapeutic Strategy ◽  
Malignant Tumors ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
Effective Therapeutic Strategy ◽  
Cancer Types ◽  
The Brain

The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling pathways, such as aldehyde dehydrogenase (ALDH), CD133, epithelial cell adhesion molecule (EpCAM), Wnt/β-catenin signaling, and Notch signaling, contribute to the initiation and progression of various liver cancer types. Importantly, CSCs are markedly resistant to conventional therapeutic approaches and current targeted therapeutics. Therefore, it is believed that selectively targeting specific markers and/or signaling pathways of hepatic CSCs is an effective therapeutic strategy for treating chemotherapy-resistant liver cancer. Here, we provide an overview of the current knowledge on the hepatic CSC hypothesis and discuss the specific surface markers and critical signaling pathways involved in the development and maintenance of hepatic CSC subpopulations.

Anticancer Immunotoxins, Challenges, and Approaches

2020 ◽  
Vol 26 ◽  
Author(s):  
Maryam Dashtiahangar ◽  
Leila Rahbarnia ◽  
Safar Farajnia ◽  
Arash Salmaninejad ◽  
Arezoo Gowhari Shabgah ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Antibody Fragment ◽  
Clinical Use ◽  
Multiple Cancer ◽  
Main Obstacle ◽  
Cancer Types ◽  
Recombinant Immunotoxins ◽  
Cancerous Cells ◽  
High Immunogenicity ◽  
Novel Therapeutic

: The development of recombinant immunotoxins (RITs) as a novel therapeutic strategy has made a revolution in the treatment of cancer. RITs are resulting from the fusion of antibodies to toxin proteins for targeting and eliminating cancerous cells by inhibiting protein synthesis. Despite indisputable outcomes of RITs regarding inhibiting multiple cancer types, high immunogenicity has been known as the main obstacle in the clinical use of RITs. Various strategies have been proposed to overcome these limitations, including immunosuppressive therapy, humanization of the antibody fragment moiety, generation of immunotoxins originated from endogenous human cytotoxic enzymes, and modification of the toxin moiety to escape the immune system. This paper devoted to reviewing recent advances in the design of immunotoxins with lower immunogenicity.

lncRNAs as Potential Targets in Small Cell Lung Cancer: MYC -dependent Regulation

2020 ◽  
Vol 20 (17) ◽  
pp. 2074-2081
Author(s):  
Onur Tokgun ◽  
Pervin E. Tokgun ◽  
Kubilay Inci ◽  
Hakan Akca
Keyword(s):  
Lung Cancer ◽  
Stem Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Strategy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Shrna Vector

Background: Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy. MYC family oncogenes are amplified and overexpressed in 20% of SCLCs, showing that MYC oncogenes and MYC regulated genes are strong candidates as therapeutic targets for SCLC. c-MYC plays a fundamental role in cancer stem cell properties and malignant transformation. Several targets have been identified by the activation/repression of MYC. Deregulated expression levels of lncRNAs have also been observed in many cancers. Objective: The aim of the present study is to investigate the lncRNA profiles which depend on MYC expression levels in SCLC. Methods: Firstly, we constructed lentiviral vectors for MYC overexpression/inhibition. MYC expression is suppressed by lentiviral shRNA vector in MYC amplified H82 and N417 cells, and overexpressed by lentiviral inducible overexpression vector in MYC non-amplified H345 cells. LncRNA cDNA is transcribed from total RNA samples, and 91 lncRNAs are evaluated by qRT-PCR. Results: We observed that N417, H82 and H345 cells require MYC for their growth. Besides, MYC is not only found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2, cyclinD1, Sox2, Aldh1a1, and N-Cadherin), but also found to regulate lncRNAs. With this respect, expressions of AK23948, ANRIL, E2F4AS, GAS5, MEG3, H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1, and BC200 were observed to be in parallel with MYC expression, whereas expressions of Malat1, PTENP1, Neat1, UCA1, SNHG3, and SNHG6 were inversely correlated. Conclusion: Targeting MYC-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study indicated the importance of identifying MYC-regulated lncRNAs and that these can be utilized to develop a therapeutic strategy for SCLC.

scholarly journals Cancer Vaccines: Promising Therapeutics or an Unattainable Dream

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 668
Author(s):  
Howard Donninger ◽  
Chi Li ◽  
John W. Eaton ◽  
Kavitha Yaddanapudi
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Tumor Immunity ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Host Immune System ◽  
Tumor Type ◽  
Therapeutic Vaccines ◽  
Cancer Types ◽  
Prophylactic Vaccines

The advent of cancer immunotherapy has revolutionized the field of cancer treatment and offers cancer patients new hope. Although this therapy has proved highly successful for some patients, its efficacy is not all encompassing and several cancer types do not respond. Cancer vaccines offer an alternate approach to promote anti-tumor immunity that differ in their mode of action from antibody-based therapies. Cancer vaccines serve to balance the equilibrium of the crosstalk between the tumor cells and the host immune system. Recent advances in understanding the nature of tumor-mediated tolerogenicity and antigen presentation has aided in the identification of tumor antigens that have the potential to enhance anti-tumor immunity. Cancer vaccines can either be prophylactic (preventative) or therapeutic (curative). An exciting option for therapeutic vaccines is the emergence of personalized vaccines, which are tailor-made and specific for tumor type and individual patient. This review summarizes the current standing of the most promising vaccine strategies with respect to their development and clinical efficacy. We also discuss prospects for future development of stem cell-based prophylactic vaccines.

scholarly journals Dual Roles of the Activin Signaling Pathway in Pancreatic Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 821
Author(s):  
Wanglong Qiu ◽  
Chia-Yu Kuo ◽  
Yu Tian ◽  
Gloria H. Su
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Critical Role ◽  
Genetic Mutations ◽  
Cancer Genetic ◽  
Dual Roles ◽  
Activin Signaling ◽  
Physiological Processes ◽  
Cancer Types ◽  
Related Proteins

Activin, a member of the TGF-β superfamily, is involved in many physiological processes, such as embryonic development and follicle development, as well as in multiple human diseases including cancer. Genetic mutations in the activin signaling pathway have been reported in many cancer types, indicating that activin signaling plays a critical role in tumorigenesis. Recent evidence reveals that activin signaling may function as a tumor-suppressor in tumor initiation, and a promoter in the later progression and metastasis of tumors. This article reviews many aspects of activin, including the signaling cascade of activin, activin-related proteins, and its role in tumorigenesis, particularly in pancreatic cancer development. The mechanisms regulating its dual roles in tumorigenesis remain to be elucidated. Further understanding of the activin signaling pathway may identify potential therapeutic targets for human cancers and other diseases.

Sex Differences in Cancer Genomes: Much Learned, More Unknown

Endocrinology ◽  
2021 ◽  
Author(s):  
Chenghao Zhu ◽  
Paul C Boutros
Keyword(s):  
Sex Differences ◽  
Precision Medicine ◽  
Cause Of Death ◽  
Clinical Presentation ◽  
Response To Treatment ◽  
Critical Gap ◽  
Cancer Genomes ◽  
Cancer Initiation ◽  
Cancer Types ◽  
Key Resources

Abstract Cancer is a leading cause of death worldwide. Sex influences cancer in a bewildering variety of ways. In some cancer types it affects prevalence, in others genomic profiles, or response to treatment, or mortality. In some sex seems to have little or no influence. How and when sex influences cancer initiation and progression remain a critical gap in our understanding of cancer, with direct relevance to precision medicine. Here, we note several factors that complicate our understanding of sex differences: representativeness of large cohorts, confounding with features like ancestry, age and obesity, and variability in clinical presentation. We summarize the key resources available to study molecular sex differences, and suggest some likely directions for improving our understanding of how patient sex influences cancer behaviour.

Sign in / Sign up

Export Citation Format

Share Document