The field of breast cancer is a priority for new drug development, with a large number of new drugs entering clinical studies or coming to market every year. With the increasing level of breast cancer research in China and the growing market share, more and more breast cancer therapeutics are choosing to conduct clinical studies in China, even from Phase I clinical studies. More encouragingly, there are also a number of new class I drugs developed by Chinese scholars in the field of breast cancer treatment, which are not only expected to bring clinical benefits to Chinese patients, but also show the overall improvement of medical standard in China. The following is a brief introduction of some of the major new drugs currently being developed in China for the treatment of breast cancer and their related clinical research projects, which are mainly targeted therapeutic drugs, but also include chemotherapeutic drugs and endocrine drugs. Afatinib (BIBW2992) BIBW 2992 is a novel dual-targeted, irreversible EGFR/HER-2 tyrosine kinase inhibitor developed by Boehringer Ingelheim. Phase II clinical studies have initially demonstrated clinical activity of BIBW 2992 in EGFR-mutated non-small cell lung cancer and HER-2-positive breast cancer, as well as in patients with HER-2 overexpressing metastatic breast cancer who were previously refractory to trastuzumab treatment. BIBW 2992, an irreversible EGFR/HER-2 tyrosine kinase inhibitor, may be useful in overcoming the effects of trastuzumab therapy on metastatic HER-2-positive breast cancer. inhibitor, may be more advantageous in overcoming trastuzumab resistance. We are currently conducting an international multicenter phase III clinical study to evaluate the efficacy of BIBW 2992 in combination with chemotherapy in metastatic HER-2 overexpressed breast cancer after trastuzumab treatment failure. 2. Neratinib (HKI272) HKI272 is an irreversible EGFR/HER-2 tyrosine kinase inhibitor, developed by Pfizer. Phase I and II clinical studies have been completed in our hospital, which initially confirmed the significant clinical efficacy and controllable adverse effects of HKI272 in HER-2-positive breast cancer, with an efficiency of 26-64% for single agent and even up to 80% for the combination, and also showed significant efficacy in breast cancer patients who failed after trastuzumab treatment. We are currently conducting an international multicenter phase III clinical study of HKI272 in combination with paclitaxel for the first-line treatment of HER-2-positive locally recurrent or metastatic breast cancer. 3. Everolimus Everolimus is a multifunctional mammalian target of rapamycin (mTOR) inhibitor. mTOR is an intracellular serine/threonine kinase, a central intracellular regulator that senses changes in intracellular growth factors and nutrient energy signals. mTOR is a key downstream signaling molecule of many signaling pathways, involving ER, EGFR, HER-2 and other tumor key signaling pathways. Theoretically, as a downstream molecule of HER-2 signaling pathway, inhibition of mTOR can overcome anti-HER-2 treatment resistance caused by mTOR upstream gene abnormalities (e.g. PI3K mutation, PTEN deletion, etc.), and also enhance the efficacy of anti-HER-2 treatment. In fact, it has also been demonstrated in previous clinical studies that everolimus in combination with trastuzumab can enhance the efficacy and overcome drug resistance. The drug is developed by Novartis, in oral dosage form, and is currently undergoing two phase III clinical studies in our hospital, one is “Everolimus in combination with trastuzumab and paclitaxel for the first-line treatment of HER-2-positive locally advanced or metastatic breast cancer”, and the other is “Everolimus in combination with trastuzumab and The other is “everolimus combined with trastuzumab and vincristine in second and third line for HER-2 positive locally advanced or metastatic breast cancer”. Cipatinib Cipatinib is a small molecule multi-target, 4-anilinoquinazoline-based receptor tyrosine kinase inhibitor that inhibits the epidermal growth factor receptor (ErbB1/EGFR) and human epidermal factor receptor 2 (ErbB2/HER-2). Its mechanism of action is similar to lapatinib, an original new antitumor drug developed independently by Jiangsu Haosen Pharmaceutical. The preliminary preclinical efficacy study found that cipatinib tosylate has significant efficacy on a variety of human tumor cell lines with high expression of EGFR and HER-2 and human tumor nude mouse transplantation model; and the preclinical toxicology study results more fully show that it has less liver toxicity and skin toxicity than lapatinib and is well tolerated. The foreign counterpart, lapatinib, was approved for marketing by the U.S. Food and Drug Administration (FDA) on March 13, 2007, in combination with capecitabine for the treatment of advanced or metastatic breast cancer with HER-2 overexpression. Cipatinib is currently in a phase Ia clinical study at our hospital, mainly to study the tolerability and pharmacokinetic characteristics of the drug in the treatment of advanced breast cancer. 5.Apatinib The chemical name of Apatinib is N-[4-(cyanocyclopentyl)phenyl]{2-[(4-pyridinylmethyl)amino] (3-pyridine)}carboxamide mesylate, which is a small molecule VEGFR inhibitor, mainly inhibits the activity of VEGFR2, but also has certain inhibitory effect on VEGFR1 and RET. The drug was developed by Jiangsu Hengrui Pharmaceutical Company and is currently in phase II clinical trial at our hospital to evaluate the efficacy and safety of apatinib in the treatment of advanced triple-negative breast cancer. As a special subtype of breast cancer, triple-negative breast cancer accounts for about 10%-20% of all breast cancers, its clinical course is aggressive and its prognosis is often worse than other breast cancer subtypes. Triple-negative breast cancer has poor efficacy for endocrine therapy and anti-HER-2 treatment, and anti-angiogenic therapy is now considered to be effective for this type of tumor. Trastuzumab is the world’s first targeted therapy drug targeting HER-2, which was approved by FDA in 1998. Meanwhile, for patients who have progressed after trastuzumab treatment, many studies have also confirmed that the continued use of trastuzumab can bring further clinical benefit to patients. Therefore, we are currently conducting a national multicenter, single-arm, open phase IV clinical study to evaluate the efficacy and safety of continued first-line treatment with trastuzumab combined with paclitaxel drug in HER-2-positive metastatic breast cancer that has recurred after trastuzumab (neo) adjuvant therapy. 7.Epothilone B Epothilone B is a new class of microtubule stabilizer, which has the effect of promoting GTP-dependent microtubule protein polymerization to form microtubules and has a stabilizing effect on microtubules; while inhibiting the depolymerization of microtubules by stabilizing the process of microtubule assembly, leading to abnormal arrangement of microtubule bundles and formation of stellate bodies, which in turn inhibits the formation of normal mitotic spindle of cells, thus inhibits the growth of tumor cells and even induces their death. The drug was developed by Hazen Pharmaceuticals and is structurally similar to Epothilone B (EPO906), which was developed by Novartis and is currently in Phase II clinical studies. The same product, Epothilone D, was approved by the FDA in 2007 and can be used as a single agent or in combination with capecitabine for the treatment of locally recurrent or metastatic breast cancer. Phase I clinical study of epothilone B is currently underway in our hospital, mainly to evaluate its tolerability and pharmacokinetic characteristics, and also to preliminarily observe its anti-tumor activity. 8. Acoradin Acoradin is a selective estrogen receptor modulator, developed by |Oki Pharmaceuticals. It is a single active ingredient extracted from the herb Epimedium, chemically named 3,5,7-trihydroxy-2-(4-hydroxymethylphenyl)-8-(3-methylbutenyl-2)-1,2-benzopyran-4-one, which can specifically bind ER-α36 receptor. The known estrogen receptors can be divided into α and β isoforms, of which ER-α36 is a new homodimer of ER-α with a molecular weight of 36 kDa. ER-α36 is mainly distributed on the cell membrane and in the cell plasma, with a small amount in the nucleus, and can stimulate cell division through the non-classical estrogen membrane signaling pathway and via the MAPK/ERK signaling pathway. er-α 36 is distinguished from is ER-α (ER-α66). The anti-estrogenic drug tamoxifen is less effective in treating breast cancer patients with high ER-α 36 expression. In contrast, acoradin, the first highly specific modulator of ERα-36 receptor identified so far, shows significant tumor-suppressive activity even for tamoxifen-resistant breast cancer cells and may become a new endocrine therapeutic agent for breast cancer.