title: Cancer metastasis: issues and challenges.
abstract: Metastasis is the major cause of treatment failure in cancer patients and of cancer-related deaths. This editorial discusses how cancer metastasis may be better perceived and controlled. Based on big-data analyses, a collection of 150 important pro-metastatic genes was studied. Using The Cancer Genome Atlas datasets to re-analyze the effect of some previously reported metastatic genes-e.g., JAM2, PPARGC1A, SIK2, and TRAF6-on overall survival of patients with renal and liver cancers, we found that these genes are actually protective factors for patients with cancer. The role of epithelial-mesenchymal transition (EMT) in single-cell metastasis has been well-documented. However, in metastasis caused by cancer cell clusters, EMT may not be necessary. A novel role of epithelial marker E-cadherin, as a sensitizer for chemoresistant prostate cancer cells by inhibiting Notch signaling, has been found. This editorial also discusses the obstacles for developing anti-metastatic drugs, including the lack of high-throughput technologies for identifying metastasis inhibitors, less application of animal models in the pre-clinical evaluation of the leading compounds, and the need for adjustments in clinical trial design to better reflect the anti-metastatic efficacy of new drugs. We are confident that by developing more effective high-throughput technologies to identify metastasis inhibitors, we can better predict, prevent, and treat cancer metastasis.
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China. qianchn@sysucc.org.cn.
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, and Key Laboratory of Longevity and Aging-related Diseases, Ministry of Education, Nanning, 530021, Guangxi, P. R. China.|Department of Biology, Southern University of Science and Technology School of Medicine, Shenzhen, 518055, Guangdong, P. R. China.|Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15232, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents
keywords: E-cadherin; EMT; JAM2; Metastasis; PPARGC1A; SIK2; TRAF6