NO015.20190112.TrendsPharmacolSc

原文链接：Lessons Learned from Two Decades of Anticancer Drugs

摘要全文

Tremendous efforts have been made to elucidate the basis of cancer biology with the aim of promoting anticancer drug development. Especially over the past 20 years, anticancer drug development has developed from conventional cytotoxic agents to target-based and immune-related therapies. Consequently, more than 200 anticancer drugs are available on the market. However, anticancer drug development still suffers high attrition during the later phases of clinical development and is considered to be a difficult and risky therapeutic category within the drug development arena. The disappointing performance of investigational anticancer candidates implies that there are some shortcomings in the translation of preclinical in vitro and in vivo models to humans, and that heterogeneity in the patient population presents a significant challenge. Here, we summarize both successful and failed experiences in anticancer development during the past 20 years and help identify why the current paradigm may be suboptimal. We also offer potential strategies for improvement.

论点摘录

1. Patients with cancer suffer high mortality rates, which range from 1.1% for prostate cancer to 92.3% for pancreatic cancer within 5 years of cancer diagnosis.（诊断后5年的死亡率：前列腺癌最低，为1.1%，胰腺癌最高，为92.3%）
2. Less than 5% of anticancer compounds developed reach the market.
3. The ultimate task for an anticancer drug is to kill the tumor cells and/or control their proliferation to prolong patient survival and improve their quality of life.（抗肿瘤药物的终极目标）
4. By contrast, approximately 45% of rare diseases are rare oncological diseases, some of which have no treatment options available on the market.（罕见病中的45%左右都是癌症，这些癌症中的一部分在市场上都是没有可选择的治疗方案的）
5. There is no obvious correlation between the number of drugs to treat a particular cancer and the 5-year survival rate and/or estimated new cases for different cancer types, which may imply that developments in treatment are mainly based on the understanding of cancer nature history and on our accumulated knowledge of the pathogenesis and etiology of cancer.（癌症的药物数量与5年生存率以及预估的新发病例没有明显的相关性，这也许意味着，药物的研发主要还是基于对于癌症本身的了解）
6. ClinicalTrials.gov数据库中约40%的试验是与“Cancers and Other Neoplasms”相关的，说明了癌症是临床试验的主要研究对象（major focus）。
7. 在NCI支持的5154个癌症相关的临床试验中，73%是癌症治疗相关的试验，其分期情况为：45% in Phase I, 53% in Phase II, 8.6% in Phase III, and only 0.6% in Phase IV，这说明很多的化合物都是处在临床试验的早期阶段，相对较少的能够进入到III期或IV期。