Cancer Genetics and Epigenetics 2018, Vol.6, No.2, 13-18
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Orapanil alone and combined with chemotherapeutic drugs obtained a high objective response rate in clinical
trials, but the risk of a second primary tumor increased due to its mechanism of inhibiting DNA repair
(Shaughnessy et al., 2011).
3.2 Targeted therapy related to tyrosine kinase inhibition
Tyrosine kinase inhibitor (TKIs) is a kind of drugs which can inhibit tyrosine kinase activity by inhibiting
phosphorylation of protein tyrosine residues to block downstream signal transduction and then inhibit tumor
growth and metastasis. Both epidermal growth factor receptor (EGFR) and vascular endothelial growth factor
receptor (VEGFR) have tyrosine kinase activity receptors, and control the proliferation, Invasion and metastasis of
tumor cells by mediating many signal pathways (Chaudhuri et al., 2016).
Existing studies have shown that EGFR inhibitors alone are difficult to achieve the purpose of anti-tumor, and
may be more suitable for use as a class of sensitizers. Bevacizumab, an inhibitor of VEFG, is the only drug
associated with FDA. However, in 2011, FDA withdrew the indication of bevacizumab in breast cancer because
several III phase clinical trials showed that its combined use of breast cancer therapy and chemotherapeutic drugs
led to a significant increase in toxicity, but no significant improvement in DFS and OS (Ho-Yen et al., 2014).
3.3 PI3K-AKT-mTOR pathway inhibitor
PI3K/Akt/mTOR pathway plays an important role in the proliferation, vascular growth and metastasis of tumor
cells. The pathway is activated in breast cancer. Its inhibitor can inhibit the growth of breast cancer and induce
apoptosis of cancer cells. It is expected to be a new target for targeted therapy of TNBC (Banerji et al., 2012).
3.4 Serotonine protein kinase-related targeting drugs
PIM1 kinase is a serotonine protein kinase, and it has been shown that PIM1 kinase inhibitor can be used as a new
target therapy for TNBC patients (Horiuchi et al., 2016). The expression of PIM1 in TNBC tissues is higher than
that in normal breast tissues and receptor-positive breast cancer tissues, and PIM1 plays an important role in the
growth and proliferation of MYC expressed TNBC cells (Fara et al., 2016).
The use of these monoclonal antibodies or inhibitors is of limited value, and only when combined with
chemotherapeutic drugs or multiple targeted drugs can the objective response rate or survival be significantly
improved. Continue to look for new markers of triple negative breast cancer, the goal is to improve the overall
survival of patients, it is still the direction of treatment of triple negative breast cancer in the future.
4 Immunotherapy Therapy
Tumor immunotherapy is to control and kill tumor cells by stimulating or mobilizing the immune system of the
body and enhancing the immunity of tumor microenvironment, which has high specificity and little damage to the
normal tissues of the body. In recent ten years, new immunotherapy drugs have been emerging. At present, six
kinds of drugs have been approved by FDA for the treatment of malignant tumors.
The most promising immunotherapeutic drug is the immune checkpoint inhibitor (ICPI). Immune checkpoint is a
costimulatory molecule that inhibits signal pathway. In normal circumstances, it can inhibit the function of T cells,
participate in negative regulation of immune system, and avoid the damage of autoimmune reaction to the body.
But in tumor tissue, it may be used by tumor to form immune escape. The principle of immunological checkpoint
inhibitor in the treatment of tumor is to remove the negative regulation of T cell activity by these costimulatory
molecules and to enhance the cytotoxicity of T cell to tumor (Roberto et al., 2018).
The combination of chemotherapy and ICPI may have synergistic effect, which has been confirmed by many
preclinical studies. These results show that immunotherapy may be effective in breast cancer and may be the best
in patients with advanced TNBC.
The most studied targets of ICPI include cytotoxic T lymphocyte associated antigen 4 (CTLA-4), programmed
death factor 1 (PD-1) and programmed death factor ligand 1 (PD-L1). PD-1 is an important immunosuppressive
