Over the past 2 decades, there has been an extraordinary progress in the regimens developed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1) are commonly recommended anti-HER2 target agents by the U.S. Food and Drug Administration. This review summarizes the most significant and updated research on clinical scenarios related to HER2-positive breast cancer management in order to revise the guidelines of everyday clinical practices. In this article, we present the data on anti-HER2 clinical research of neoadjuvant, adjuvant, and metastatic studies from the past 2 decades. We also highlight some of the promising strategies that should be critically considered. Lastly, this review lists some of the ongoing clinical trials, findings of which may soon be available.

Targeted therapeutic options and future perspectives for HER2-positive breast cancer.

The efficacy of lapatinib and capecitabine in HER-2 positive breast cancer with brain metastases: A systematic review and pooled analysis

Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies. Firsthand examples are presented to illustrate the principles and advantages of such integrative design strategies for cancer treatment by exploiting 1) intracellular synergistic interactions of drug-drug and drug-nanomaterial combinations to overcome multidrug-resistant cancer, 2) the blood flow direction of the circulatory system to maximize drug delivery to the tumor neovasculature and cells overexpressing integrin receptors for lung metastases, 3) endogenous lipoproteins to decorate nanocarriers and transport them across the blood-brain barrier for brain metastases, and 4) distinct pathological factors in the tumor microenvironment to develop pH- and oxidative stress-responsive hybrid manganese dioxide nanoparticles for enhanced radiotherapy. Regarding the application in diabetes management, a nanotechnology-enabled closed-loop insulin delivery system was devised to provide dynamic insulin release at a physiologically relevant time scale and glucose levels. These examples, together with other research results, suggest that utilization of the interplay of pharmacology, (patho-)physiology and nanotechnology is a facile approach to develop innovative drug delivery systems and therapies with high efficiency and translational potential.

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Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy - an illustration with firsthand examples.

Pregnane X receptor mediates sorafenib resistance in advanced hepatocellular carcinoma.

// Xiao-Xiao Ding 1, * , Qing-Ge Zhu 1, * , Shi-Ming Zhang 1, * , Lei Guan 1 , Ting Li 1 , Lei Zhang 1 , Shi-Yang Wang 2 , Wan-Li Ren 2 , Xue-Mei Chen 1 , Jing Zhao 1 , Song Lin 1 , Zhi-Zhen Liu 1 , Yan-Xia Bai 2 , Bing He 1 and Hu-Qin Zhang 1 1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, P. R. China 2 Department of Otorhinolaryngology - Head and Neck Surgery, The First Affiliated Hospital, Jiaotong University, Shaanxi 710061, P. R. China * These authors have contributed equally to this work Correspondence to: Hu-Qin Zhang, email: huqzhang@mail.xjtu.edu.cn Bing He, email: hebinghb@mail.xjtu.edu.cn Yan-Xia Bai, email: yanxiab@126.com Keywords: hepatocellular carcinoma, driver mutations, driver identification, targeted therapy, precision medicine Received: March 31, 2017     Accepted: May 10, 2017     Published: June 06, 2017 ABSTRACT Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called “driver mutations”. The discovery of driver mutations provides a novel precision medicine strategy for late stage HCC, called targeted therapy. In this review, we summarized currently discovered driver mutations and corresponding signaling pathways, made an overview of identification methods of driver mutations and genes, and classified targeted drugs for HCC. The knowledge of mutational landscape deepen our understanding of carcinogenesis and promise future precision medicine for HCC patients.

Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2- occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P 0.05).

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study.

// Peisi Kou 1,2,* , Yan Zhang 2,* , Wenbo Shao 4 , Hui Zhu 2 , Jingze Zhang 2 , Haiyong Wang 2 , Li Kong 2 and Jinming Yu 2,3,1 1 Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China 3 School of Medicine and Life Sciences, University of Jinan - Shandong Academy of Medical Sciences, Jinan, China 4 Department of Intervention, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China * These authors have contributed equally to this work Correspondence to: Jinming Yu, email: // Keywords : hepatocellular carcinoma, apatinib, targeted therapy Received : September 06, 2016 Accepted : January 04, 2017 Published : January 18, 2017 Abstract Apatinib is a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. Previous studies have suggested that apatinib is safe and effective in some solid tumors. We report one case with advanced hepatocellular carcinoma (HCC), who received apatinib combined with transhepatic arterial chemotherapy and embolization (TACE), and chemotherapy respectively. TACE was administered three times once a month, using lipiodol 10ml, oxaliplatin 150mg, and tegafur 1g. The dose of apatinib was 500 mg/d from day 4 to 24. After TACE, the patient received chemotherapy of regimen FOLFOX4, oxaliplatin intravenously at 85 mg/m 2 on day 1, calcium levofolinate 200 mg/m 2 on day 1 and 2, 5-fluorouracil 400 mg/m 2 intravenously and 5-fluorouracil 600 mg/m 2 intravenously pumped for 22h on day 1 and 2, cycled every two weeks for seven cycles. He took concurrently apatinib with a dose of 500mg daily from 1 to 10 days per cycle. He was confirmed as partial response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST). The level of serum alpha-fetoprotein (AFP) decreased from 60500 ng/ml to 12.7 ng/ml, and the progression free survival (PFS) time was more than eight months. It indicated that apatinib may be a superior choice for HCC patients.

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Significant efficacy and well safety of apatinib in an advanced liver cancer patient: a case report and literature review.

// Haiyong Wang 1 , Jingze Zhang 1 , Fang Shi 1 , Chenyue Zhang 2 , Qinghua Jiao 3 , Hui Zhu 1 1 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan 250117, China 2 Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China 3 Cancer Center, The Second Hospital of Shandong University, Shandong 250033, China Correspondence to: Haiyong Wang, email: wanghaiyong6688@126.com Hui Zhu, email: drzhuhui@163.com Keywords: small cell lung cancer, young, cancer specific survival, SEER Received: September 16, 2016      Accepted: March 24, 2017      Published: April 04, 2017 ABSTRACT It has been reported that younger patients with non-small cell lung cancer (NSCLC) tend to have a better prognosis. Yet, few studies have focused on the clinicopathological characteristics and prognosis of young small cell lung cancer (SCLC), especially for patients with age 0.05). In conclusion, our study demonstrated that the SCLC patients with aged < 50 tended had a better survival benefit, especially for patients with AJCC stage III.

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Better cancer specific survival in young small cell lung cancer patients especially with AJCC stage III.

Background: Traditional Chinese medicine (TCM), a main form of complementary and alternative medicine provides a potential possibility for demyelinating disease of the central nervous system (DDC) management and has been applied in considerable amounts of patients with this disorder. Nevertheless, powerful real-world evidences regarding the epidemiological and clinical characteristics, safety, and outcomes of TCM in DDC are lacking. The primary objective of the Demyelinating Diseases of the Central Nervous System Registry for Patients with Traditional Chinese Medicine (DATE-TCM) is to create an organized multicenter data collection structure to define integrative characteristics of DDC patients treated with TCM in an endeavor to fill these knowledge gaps to better inform clinical care and health policy. Method: This study provides a prospective and voluntary registry by using a web-based system. Baseline data will be recorded and subsequently regular follow-up visits will be implemented every 3–6 months for a total of 5 years. The primary outcome is Annualized Aggregate Relapse Rate at 5-year follow-up. Results: DATE-TCM is currently designed to capture the multidimensional (epidemiologic, demographic, clinical, etc.) features of DDC patients receiving TCM treatment, the type and long-term safety and efficacy of TCM intervenes in the DDC populations, as well as the interaction of TCM treatments and disease modifying therapies in the management of DDC, aiming to include 2000 eligible adult DDC patients with TCM intervenes from 35 participating centers, covering 77.4% of provincial administrative regions of mainland China. Conclusion: DATE-TCM is the first, largest, most geographically extensive, and standard registry-based observational study that systematically document the real-world data regarding the TCM application in the DDC populations, which will be extraordinarily important for clarifying the comprehensive characteristics and outcomes of TCM in DDC, further shed light on standardizing and optimizing the TCM measures for DDC management and establishing evidence-based clinical practice guidelines for TCM application in DDC.

Demyelinating diseases of the central nervous system registry for patients with traditional Chinese medicine: Rationale and design of a prospective, multicenter, observational study

Jingze Zhang

Papers

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study.

Significant efficacy and well safety of apatinib in an advanced liver cancer patient: a case report and literature review.

Better cancer specific survival in young small cell lung cancer patients especially with AJCC stage III.

Demyelinating diseases of the central nervous system registry for patients with traditional Chinese medicine: Rationale and design of a prospective, multicenter, observational study