Cancer is a serious threat to the public health of the malignant disease. In the past 10 years, with the progress of basic medical research and clinical treatment model changes and some new Antitumor drug target discovery, Antitumor drug research and development has undergone tremendous changes - from the traditional cytotoxicity Class of drugs turned to non-cytotoxic targeted drug development. In this paper, from January 1, 2005 to December 31, 2011, domestic and foreign Antitumor drug research report was reviewed and reviewed, from summing up and analysis of the past 10 years, Antitumor drug research and development of the main progress and future trends , With a view to the Antitumor drug research and development related personnel to provide a reference.
Because of the refractory disease and the urgency of clinical needs, Antitumor drugs has been a hot research and development of innovative drugs. Especially in recent years, domestic and foreign major pharmaceutical companies have increased investment in anti-cancer drug research and development, some of the original non-cancer drug companies have joined the ranks of the industry, through mergers and acquisitions, cooperation and other ways to expand their own tumor products line. According to statistics, foreign companies in 2010 to enter the clinical trial of tumor drug compounds is about 2.5 times in 2005; the State Food and Drug Administration (SFDA) accepted Antitumor drug claims accounted for the proportion of all innovative drugs, from 2005 10% Rose to about 40% in 2010 - both domestic and new drugs, or the number of new drugs to declare the number of doubled. In the national major new drug creation special, the declared candidate compounds also nearly 60% for the Antitumor drugs.
Molecular targeting research has become mainstream
Traditional cytotoxic drugs (which can specifically block cell division and cause cell death), while killing tumor cells, also destroy normal human cells, with treatment-related toxicity, and may even shorten patient life. Therefore, research and development of Antitumor drugs that selectively kill or inhibit the new mechanism of tumor cells has become the target of many researchers.
The rapid development of molecular biology and cell biology reveals many molecular mechanisms of tumor cell growth, proliferation and regulation. On this basis, a variety of Antitumor new drug targets have been found. These targets are relatively specific and can block tumor growth or reduce the effect on normal cells, the toxicity is relatively light. Thus, Antitumor drug development from cytotoxic drugs and broad-spectrum cell cycle inhibitors to more specific cell signal transduction inhibitors, including macromolecular monoclonal antibodies and small molecule compounds. Which in turn small molecule tyrosine kinase inhibitor (TKI) for the development of the most popular class of Antitumor drugs. Prior to 2005, SFDA accepted TKI class of new drugs less than 5, and by the end of 2011, the total amount of new drugs reported more than 50.
At present, TKI targets mainly focus on EGFR, VEGFR, PDGFR, SRC, ABL and several other members of the tyrosine kinase family, the current success of the product is also aimed at these targets. Hepatocyte growth factor (HGF) and its receptor c-Met protein are also a more common target, and are likely to be the next successful target. Because tumor growth and survival not only rely on a receptor or a signaling pathway, a single agent acting on multiple targets may produce multiple pharmacological activities, so as to achieve a number of links in the signal pathway inhibition, therefore, the role TKI at multiple targets appears to be the main development direction of the current tumor drug (approximately 3/4).
Second, many pharmaceutical companies targeted drug product lines have significant overlap, for the same target may have multiple drugs are being developed. At the same time, there are a number of drugs for the same indications are being developed (mostly concentrated in the high incidence of large market potential of the tumor, non-small cell lung cancer that is the largest NSCLC). On the other hand, research in the field of small indications has become "crowded" because of the intense competition in the field of high-risk tumors, which has led to more corporate research to or from other rare tumors. For example, since Sorafeni was approved by SFDA in December 2005, the number of new drug applications in the area of kidney cancer increased significantly. Therefore, how in the current competitive situation, to develop a reasonable R & D strategy, identify the appropriate clinical positioning is quite important.