Antibody-drug conjugates in HER2-positive breast cancer / 中华医学杂志(英文版)

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.

Profile of gene mutations and targeted treatment of brain metastases in breast cancer / 国际肿瘤学杂志

Brain metastasis (BM) is considered one of the major causes of mortality in breast cancer patients.BM develops more frequently in triple-negative breast cancer and human epidermal growth factor receptor 2 (HER2)-positive breast cancers,while the incidence of BM in hormone receptor positive is much lower.Mutations and expression of BM of breast cancer are differ from their primay tumors.Importantly,some therapeutic actionable mutations can be present in the BM while not in the primary tumors.Current targeted therapeutics in BM of breast cancers are limited,and drugs used have proven effects on the primary tumors but lack specificity for the BM.The identification of genomic and expressional alterations specific to BM are crucial to the development of BM specific targeted therapies.

Analysis of intra-tumor heterogeneity in breast cancer precision medicine / 国际肿瘤学杂志

As a breakthrough of precision medicine,intra-tumor heterogeneity is a research hotspot and is correlated to tumorigenesis,metastasis and resistance to therapies.In breast cancer,evidence of intra-tumor heterogeneity has been documented by numerous studies and it is the main obstacle to find ideal tumor markers and personalized medicine.Further analysis including the feature and generation mechanism of intra-tumor heterogeneity and the methods to assessment intra-tumor heterogeneity in the clinic are the key to cancer precision medicine.

Analysis of intra-tumor heterogeneity in breast cancer precision medicine / 国际肿瘤学杂志

As a breakthrough of precision medicine,intra-tumor heterogeneity is a research hotspot and is correlated to tumorigenesis,metastasis and resistance to therapies.In breast cancer,evidence of intra-tumor heterogeneity has been documented by numerous studies and it is the main obstacle to find ideal tumor markers and personalized medicine.Further analysis including the feature and generation mechanism of intra-tumor heterogeneity and the methods to assessment intra-tumor heterogeneity in the clinic are the key to cancer precision medicine.

Biomarkers of Everolimus Sensitivity in Hormone Receptor-Positive Breast Cancer / 한국유방암학회지

Activation of the mammalian target of rapamycin (mTOR) signaling pathway is an important mechanism of resistance to endocrine therapy in breast cancer. Everolimus, an mTOR inhibitor, has been shown to increase the efficacy of endocrine therapy and overcome resistance to endocrine therapies. Clinical studies have suggested that everolimus combined with endocrine therapy prolongs progression-free survival in hormone receptor-positive breast cancer patients. However, because breast cancer includes a group of highly heterogeneous tumors, patients may have different responses to everolimus. Therefore, finding biomarkers that can predict a patient's positive response or resistance to everolimus is critical. Numerous preclinical studies have shown that PIK3CA/PTEN mutations are predictive of sensitivity to everolimus; however, clinical trials have not confirmed the correlation between mutation status and clinical response. KRAS or BRAF mutations can bypass the phosphatidylinositol 3-kinase pathway; therefore, mutations in KRAS or BRAF may lead to resistance to mTOR inhibitors, and preclinical studies have shown that PIK3CA mutant cells which also contain KRAS mutations are resistant to everolimus. However, there are no clinical data in breast cancer patients to support this conclusion. Therefore, large-scale clinical studies are needed to identify biomarkers of efficacy and resistance to everolimus.