Introduction: Breast cancer (BC) is the most common cancer in women. About 15 to 20 percent of women with this cancer have a positive family history of this disorder. Molecular analyzes of breast cancer tumors reveal many mutations in proto-oncogenes, tumor suppressor genes, and genome repair genes, especially double-strand breaks. Although some sufferers respond to existing treatments such as the use of Herceptin and Tamoxifen, which target HER2, estrogen and progesterone receptors, and standard chemotherapy protocols as well as platinum-based chemotherapy in triple-negative cases and BRCA 1 germline mutations. but resistance to chemotherapy drugs is an important factor in breast cancer recurrence and metastasis, which can be caused by high extra tumoral and intra tumoral heterogeneity, and is a major challenge in breast cancer treatment.
Methods: This heterogeneity can be attributed to genetic and environmental factors and the presence of cancer stem cells (CSCs). The biological activities of CSCs are regulated by several potent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. The Nanog gene First discovered in ESCs, Nanog has multipotent transcriptional regulatory functions and normal self-renewal. Although Nanog is silenced in normal somatic cells, its abnormal expression has been reported in human cancers such as breast cancer, cervical cancer, brain cancer, colon cancer, head and neck cancer, lung cancer, and gastric cancer. The emergence of immunotherapy as a valuable anticancer strategy potentially makes it an effective approach to target CSCs. One of the important strategies that has received much attention today is the use of monoclonal antibodies. These molecules, with their direct inhibitory effects and the capacity to induce antibody-dependent cytotoxicity (ADCC) in cancer cells, mAb-linked drug compounds that deliver cytotoxic agents have been proven as a practical strategy for cancer treatment. ADCs are a complex consisting of a monoclonal antibody and an anticancer drug, which are connected by a linker. Antibodies in ADC contain a chimeric or human core body that reduces both acute hypersensitivity reactions and production of neutralizing anti-drug Abs. The ideal mAb target should be a cell surface protein that is exclusively expressed on tumor cells to limit the risk of systemic toxicity. In this regard, antigens expressed on solid tumors are often also expressed on normal cells. Therefore, such antigens are defined as "tumor-associated" rather than "tumor-specific". Consequently, for all these compounds, toxicity may occur according to the spectrum of specific target expression by normal cells (on-target-off-tumor toxicity) and cancer cells (on-target-on-tumor toxicity).
Results: A complex of ADCs induces apoptosis in cancer cells in five steps. The first stage (binding to the cell surface): ADCs can be connected to the surface of the cancer cell through the binding of the monoclonal antibody to its specific antigen (cancer antigen) and thus the antibody-antigen complex is formed. The second stage (internalization): ADCs complex can be endocytosed into the cancer cell through receptor-dependent endocytosis. The third step: separating the drug from the antibody: after the endocytosis of ADCs into the cell, ADCs are placed in the primary vesicle, which then turns into a secondary vesicle, causing the linker to break and the drug is separated from the antibody. The fourth stage (release): the drug is released into the cytoplasm. The fifth stage (cell death): the drug causes cancer cell apoptosis through various mechanisms such as interaction with DNA, microtubules or enzymes involved in cell proliferation.
Conclusion: The importance of paying attention to the genetic profile of breast cancer tumors and the presence of stem cell tumors is very important in choosing the treatment method, cost, and time. Novel therapies based on ADCs on an important downstream target such as the Nanog gene can be promising for many potential targets for breast cancer treatment
Keywords: Antibody-Drug Conjugate , Nanog, breast cancer