EGFRvIII: An Oncogene with Ambiguous Role.

EGFRvIII: An Oncogene with Ambiguous Role. J Oncol. 2019;2019:1092587 Authors: Rutkowska A, Stoczyńska-Fidelus E, Janik K, Włodarczyk A, Rieske P Abstract Epidermal growth factor receptor variant III (EGFRvIII) seems to constitute the perfect therapeutic target for glioblastoma (GB), as it is specifically present on up to 28-30% of GB cells. In case of other tumor types, expression and possible role of this oncogene still remain controversial. In spite of EGFRvIII mechanism of action being crucial for the design of small active anticancer molecules and immunotherapies, i.e., CAR-T technology, it is yet to be precisely defined. EGFRvIII is known to be resistant to degradation, but it is still unclear whether it heterodimerizes with EGF-activated wild-type EGFR (EGFRWT) or homodimerizes (including covalent homodimerization). Constitutive kinase activity of this mutated receptor is relatively low, and some researchers even claim that a nuclear, but not a membrane function, is crucial for its activity. Based on the analyses of recurrent tumors that are often lacking EGFRvIII expression despite its initial presence in corresponding primary foci, this oncogene is suggested to play a marginal role during later stages of carcinogenesis, while even in primary tumors EGFRvIII expression is detected only in a small percentage of tumor cells, undermining the rationality of EGFRvIII-targeting therapies. On the other hand, EGFRvIII-positive cells are resistant to apo...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research

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Authors: Singh SP, Singh R, Gupta OP, Gupta S, Brahma Bhatt ML Abstract Mounting evidence from the literature suggests the existence of a subpopulation of cancer stem cells (CSCs) in almost all types of human cancers. These CSCs possessing a self-renewal capacity inhabit primary tumors and are more defiant to standard antimitotic and molecularly targeted therapies which are used for eliminating actively proliferating and differentiated cancer cells. Clinical relevance of CSCs emerges from the fact that they are the root cause of therapy resistance, relapse, and metastasis. Earlier, surgery, chemotherapy, and radiot...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
(Washington University School of Medicine) A new study from Washington University School of Medicine in St. Louis suggests that the age of certain immune cells used in immunotherapy plays a role in how effective it is. These cells -- natural killer (NK) cells -- appear to be more effective the earlier they are in development, opening the door to the possibility of an immunotherapy that would not utilize cells from the patient or a matched donor. Instead, they could be developed from existing supplies of what are called human pluripotent stem cells.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Autologous cellular immunotherapy or immune enhancement therapy has demonstrated some promising benefits for prostate cancer. T cell-based immunotherapy or sipuleucel-T therapy has yielded certain beneficial r...
Source: Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Research Source Type: research
Abstract Accumulating evidences have demonstrated that the existence of breast cancer-initiating cells, which drives the original tumorigenicity, local invasion and migration propensity of breast cancer. These cells, termed as breast cancer stem cells (BCSCs), possess properties including self-renewal, multidirectional differentiation and proliferative potential, and are believed to play important roles in the intrinsic drug resistance of breast cancer. One of the reasons why BCBCs cause difficulties in breast cancer treating is that BCBCs can control both genetic and non-genetic elements to keep their niches safe...
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
CONCLUSION: BCG treatment changes the expression of many cytokines and chemokines in bladder cancer. The expression differs in 3 different cell lines and their CSCs. Immune modulation of each case differs from each other. The effectivity of BCG-based immunotherapy in bladder cancer on CSCs might decrease in combination with IL2. Our results indicate that recurrence after BCG treatment for bladder cancer may not occur mainly based on the CSCs hypothesis considering bladder cancer occurs at different loci of surface epithelium. PMID: 32192892 [PubMed - as supplied by publisher]
Source: Urologic Oncology - Category: Urology & Nephrology Authors: Tags: Urol Oncol Source Type: research
AbstractCyclin A1 is a promising antigen for T cell therapy being selectively expressed in high-grade ovarian cancer (OC) and acute myeloid leukemia (AML) stem cells. For adoptive T cell therapy, a single epitope has to be selected, with high affinity to MHC class I and adequate processing and presentation by malignant cells to trigger full activation of specific T cells. In silico prediction with three algorithms indicated 13 peptides of Cyclin A1 9 to 11 amino acids of length to have high affinity to HLA-A*02:01. Ten of them proved to be affine in an HLA stabilization assay using TAP-deficient T2 cells. Their immunogenic...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Abstract Cancer stem cells represent a rare subpopulation of cancer cells carrying self-renewal and differentiation features in the multi-step tumorigenesis, tumor recurrence and metastasis. Pro-inflammatory stress is highly associated with cancer stemness via induction of cytokines, tumor-promoting immune cells and cancer stemness-related signaling pathways. This review summarizes the major pro-inflammatory factors affecting cancer stem cell characteristics and the critical immunotherapeutic strategies to eliminate cancer stem cells. PMID: 32148202 [PubMed - as supplied by publisher]
Source: Current Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Curr Stem Cell Res Ther Source Type: research
(Wyss Institute for Biologically Inspired Engineering at Harvard) Harvard University's Wyss Institute of Biologically Inspired Engineering and its collaborating institutions, the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), Dana-Farber Cancer Institute (Dana-Farber), and Harvard's Department of Stem Cell and Regenerative Biology, announce the formation of a new NIH-funded Immuno-Engineering to Improve Immunotherapy (i3) Center.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Adoptive T Cell Therapy (ACT) is a form of cancer immunotherapy. It consists of harvesting Tumor Infiltrated Lymphocytes (TIL), screening for TIL which display tumor antigen-specific T-cell receptors (TCR), expanding these in vitro, and reinfusing into the patient for treatment. While ACT has proven effective in treating various cancer types, it is a laborious procedure as the harvested TIL population has generally limited expansion and a finite lifespan.Researchers at the National Cancer Institute (NCI) Surgery Branch improved identification and isolation of the tumor antigen-specific TCR by reprogramming TIL into induced...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
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