Breast cancer is a promising target for vaccination using cancer-testis antigens known to elicit immune responses

Taylor, Mark A.; Bolton, Louise; Johnson, Peter; Elliott, Tim; Murray, Nick

doi:10.1186/bcr1749

Cited by 20 publications

(11 citation statements)

References 12 publications

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“…CTAs are involved in cellular proliferation, migration/motility, colonization, and cell division in normal germ cells, while in cancer cells, CTAs have been implicated in sustenance of growth, maintaining nutrient and oxygen supply through the activation of angiogenesis, evading apoptotic cell death, increase in tissue invasiveness and metastasis, and development of resistance to anti-cancer drugs [214]. In breast cancer, CTAs, such as MAGE-1, AKAP4, NY-BR-1, CTAG1, BAGE1, MAGE-A10, SP17, NY-ESO-1, and MAGE-A, were found to play important roles in activating cell proliferation, inhibition of apoptosis, and promoting tissue invasion and metastasis [5,[215][216][217][218][219][220][221][222]. The CTA, AKAP4, in particular seems to be an interesting candidate for a serum-based diagnostic test for the early detection and diagnosis of breast cancer [221].…”

Section: Metformin and Breast Cancer Biomarkersmentioning

confidence: 99%

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

et al. 2019

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Interest has grown in studying the possible use of well-known anti-diabetic drugs as anti-cancer agents individually or in combination with, frequently used, chemotherapeutic agents and/or radiation, owing to the fact that diabetes heightens the risk, incidence, and rapid progression of cancers, including breast cancer, in an individual. In this regard, metformin (1, 1-dimethylbiguanide), well known as ‘Glucophage’ among diabetics, was reported to be cancer preventive while also being a potent anti-proliferative and anti-cancer agent. While meta-analysis studies reported a lower risk and incidence of breast cancer among diabetic individuals on a metformin treatment regimen, several in vitro, pre-clinical, and clinical studies reported the efficacy of using metformin individually as an anti-cancer/anti-tumor agent or in combination with chemotherapeutic drugs or radiation in the treatment of different forms of breast cancer. However, unanswered questions remain with regards to areas such as cancer treatment specific therapeutic dosing of metformin, specificity to cancer cells at high concentrations, resistance to metformin therapy, efficacy of combinatory therapeutic approaches, post-therapeutic relapse of the disease, and efficacy in cancer prevention in non-diabetic individuals. In the current article, we discuss the biology of metformin and its molecular mechanism of action, the existing cellular, pre-clinical, and clinical studies that have tested the anti-tumor potential of metformin as a potential anti-cancer/anti-tumor agent in breast cancer therapy, and outline the future prospects and directions for a better understanding and re-purposing of metformin as an anti-cancer drug in the treatment of breast cancer.

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Section: Metformin and Breast Cancer Biomarkersmentioning

confidence: 99%

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

et al. 2019

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“…Although our lack of knowledge about the biological function of CTAs complicates their utilisation, the use of CTAs as targets for the vaccination of breast cancer has been under debate widely the last years [41]. …”

Section: Discussionmentioning

confidence: 99%

Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications

et al. 2013

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BackgroundCancer–testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors.MethodsThe reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210 randomly selected primary invasive breast cancers in order to study the diversity of different CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were correlated to clinico-pathological parameters and outcome data including disease-free and overall survival.ResultsExpression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity specifically was significantly correlated to shorter overall and disease-free survival (p=0.000 and 0.024, respectively).ConclusionsOur findings suggest that M3H67 immunoreactivity could serve as potential prognostic marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define new targets for specific breast cancer therapies.

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“…Another CTA, NY-BR-1 was frequently observed in breast cancers, indicating a possibility to define new targets in breast cancer based on NY-BR-1 [210]. Taylor et al has reported that, a vaccine directed against three CTAs-CTAG1, BAGE1 and MAGE-A10, can target two-thirds of breast cancers and can specifically target cytotoxic-T-lymphocyte responses [211]. Within the more stubborn TNBCs, when compared to other forms of breast cancer, CTA -SP17 is expressed in TNBCs [212].…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

“…Additionally, MAGE-A and NY-ESO-1 was reported to be expressed in a large population of TNBCs, thereby making MAGE-A and NY-ESO-1 potential targets for the development of vaccines [215]. The frequent occurrence of specific CTAs in breast cancers indicate a possibility to define and include new targets for therapeutic intervention [210,211]. Certain CTAs were expressed in the more stubborn TNBCs [212][213][214][215].…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

Challenges and perspectives in the treatment of diabetes associated breast cancer

Samuel

Varghese

et al. 2018

Cancer Treatment Reviews

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Type 2 diabetes mellitus is one of the most common chronic disease worldwide and affects all cross-sections of the society including children, women, youth and adults. Scientific evidence has linked diabetes to higher incidence, accelerated progression and increased aggressiveness of different cancers. Among the different forms of cancer, research has reinforced a link between diabetes and the risk of breast cancer. Some studies have specifically linked diabetes to the highly aggressive, triple negative breast cancers (TNBCs) which do not respond to conventional hormonal/HER2 targeted interventions, have chances of early recurrence, metastasize, tend to be more invasive in nature and develop drug resistance. Commonly used anti-diabetic drugs, such as metformin, have recently gained importance in the treatment of breast cancer due to their proposed anti-cancer properties. Here we discuss the link between diabetes and breast cancer, the metabolic disturbances in diabetes that support the development of breast cancer, the challenges involved and future perspective and directions. We link the three main metabolic disturbances (dyslipidemia, hyperinsulinemia and hyperglycemia) that occur in diabetes to potential aberrant molecular pathways that may lead to the development of an oncogenic phenotype of the breast tissue, thereby leading to acceleration of cell growth, proliferation, migration, inflammation, angiogenesis, EMT and metastasis and inhibition of apoptosis in breast cancer cells. Furthermore, managing diabetes and treating cancer using a combination of anti-diabetic and classical anti-cancer drugs should prove to be more efficient in the treatment diabetes associated cancers.

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Breast cancer is a promising target for vaccination using cancer-testis antigens known to elicit immune responses

Cited by 20 publications

References 12 publications

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications

Challenges and perspectives in the treatment of diabetes associated breast cancer

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