What is cancer? A simplified definition of cancer is “a malignant tissue growth resulting from uncontrolled cell proliferation”. A microscopic cancer may frequently grow in the human body, but most of the time the immune system reacts and eliminates it. When the immune system is not able to eliminate the abnormal proliferation, there is development of a form of cancer, for example, liver cancer.

What causes cancer? In 1950, the WHO started to realize that migrants developed types of cancer common to their adopted countries: cancers were more often caused by exposures in the environment, rather than inherited genetic factors. In 1965, the International Agency for Research on Cancer (IARC) was created to investigate the causes of cancer in humans. Among the cancer causes discovered over time, we can mention:

• occupational and pharmaceutical agents (e.g., tobacco)
• infectious agents, notably viruses
• natural factors and non-viral infectious agents (e.g., ultraviolet radiation)

Cancer disease mutation. A mutation is an alteration of the DNA (deoxyribonucleic acid), that can cause or predispose an individual to a specific cancer disease. DNA molecules contain genes, that are regions that encode information on how to produce proteins. Proteins are macromolecules, consisting of one or more long chains of amino acids. They are responsible for carrying vital tasks for living organisms, such as pigmentation of skin, transport of elements in the organism, immune defense against infectious agents.  While a mutation is in most cases benign, or repaired by the cell machinery, in some rare cases this alteration can impact on the gene products by resulting in malfunctioning proteins, or incorrect activation of genes. These malfunctioning proteins or inaccurate activations can cause uncontrolled cell proliferation, leading in some cases to cancer.

Cancer biomarker. To characterize a cancer type, and to identify a specific therapy strategy, biomarkers are used. A biomarker is a measurable characteristic used as an indicator of a biological state. Thanks to the use of biomarkers, we have been achieving recent advances in cancer therapy and personalized medicine.

An example is the case of Triple-negative breast cancer (TNBC). In TNBC, there is poor response to classical therapies, and an aggressive behavior of the tumor (early relapse, metastatic spread, poorer survival). TNBC abnormal cells present a lack of activation of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2) genes. TNBC is more common among specific ethnicities, such as Latin, African and African American women, and accounts for approximately 10%–15% of all breast cancer cases. TNBC can be identified by the use of multiple biomarkers, i.e. a biomarker panel. This is because one single biomarker is most of the time not specific to one cancer type, or to one drug response prognosis. For the TNBC example a biomarker panel could be composed as follows:

• Biomarker 1, no estrogen receptor in cancer cells
• Biomarker 2, no progesterone receptor in cancer cells
• Biomarker 3, decrease expression of Human Epidermal Growth Factor 2

Other biomarkers can be used to identify subtypes of TNBC, such as an increased activation of the EGFR gene.

This biomarker panel implies low disease free survival, and, when the EGFR activation increases, possible treatments with erlotinib, gefitinib, or afatinib drugs.

INODE added value. Providing a question answer (QA) system over cancer research data focused on cancer biomarkers. This system is being designed to be used by worldwide researchers in order to facilitate cancer knowledge retrieval. INODE will enable cancer researchers to query in natural language and to explore cancer-related datasets such as healthy gene expression, cancer differential gene expression, cancer disease mutation and cancer biomarkers. The OncoMX team has been providing us these datasets (see https://www.oncomx.org).

References:

1. Blackadar, C. B. (2016). Historical review of the causes of cancer. World journal of clinical oncology, 7(1), 54.
2. Golemis, E. A., Scheet, P., Beck, T. N., Scolnick, E. M., Hunter, D. J., Hawk, E., & Hopkins, N. (2018). Molecular mechanisms of the preventable causes of cancer in the United States. Genes & development, 32(13-14), 868-902.
3. Feitelson, M. A., Arzumanyan, A., Kulathinal, R. J., Blain, S. W., Holcombe, R. F., Mahajna, J., … & Sharma, D. (2015, December). Sustained proliferation in cancer: Mechanisms and novel therapeutic targets. In Seminars in cancer biology (Vol. 35, pp. S25-S54). Academic Press.
4. Vafaizadeh, V., & Barekati, Z. (2020). Immuno-Oncology Biomarkers for Personalized Immunotherapy in Breast Cancer. Frontiers in Cell and Developmental Biology, 8, 162.
5. da Silva, J. L., Nunes, N. C. C., Izetti, P., de Mesquita, G. G., & de Melo, A. C. (2020). Triple negative breast cancer: A thorough review of biomarkers. Critical Reviews in Oncology/Hematology, 145, 102855.

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