The approval of cancer drugs by the United States Food and Drug Administration have increased progressively over the past two decades with a trend towards the adoption of targeted drugs which are more precise in their mechanisms of action. Advances in genetic profiling, immunohistochemical analysis of tumors, biomarker development, and a renewed appreciation of the tumor microenvironment have produced a new generation of targeted chemical and biological therapies. These innovations are the fruits of basic research in molecular and cellular biology, biochemistry, and immunology.
Purpose: To elucidate the paradigm shift in cancer drug development that has impacted the lives of patients in terms of quality of life, tumor responses, over-all survival, and potential cures.
Methods: This review is based on an examination of published literature using the National Center for Biotechnology Information (NCBI), the USFDA/National Institutes of Health (NIH) websites, USFDA approved product literature, Center Watch, industry-sponsored websites, and clinicaltrials.gov websites. Cancer drugs are classified and described based on their proposed mechanisms of action.
Results: The last two decades witnessed a paradigm shift in cancer drug development toward molecular targeted therapies and targeted drug delivery. Molecular targets include tyrosine kinase receptors, serinethreonine kinase signaling pathways, and growth factors. An increasing number of antibody-based therapies have emerged. Improvements in drug delivery include the use of albumin-bound nanoparticles for targeting the enhanced permeability and retention effects seen in tumors. Recent developments in the fields of cancer immunotherapy and gene therapy are exceedingly encouraging.
Conclusions: A review of USFDA-approved drugs and cancer drugs in clinical development, based on their mechanisms of action, is presented. The progressive shift in cancer drug development towards targeted therapies and cancer immunotherapy raises hope for improved outcomes for many types of cancer in the future.
Cancer is the second most common cause of death in the US, claiming 590,000 Americans per year, more than 1,500 people each day. The number of new cancer patients diagnosed in 2015 was over 1.6 million in the U.S. alone, not including patients with noninvasive cancers and/or skin cancers (American Cancer Society Cancer Facts, 2015). The Agency for Healthcare Research and Quality estimated the overall annual costs of cancer care at more than $227 billion (in 2012): including $89 billion for direct medical costs in the U.S. Much of the overall healthcare costs of treating cancer are derived from management of the deleterious side effects of radiation and conventional chemotherapy. Nonetheless, the chemotherapy market is currently the fastest growing segment of the pharmaceutical industry. There is a trend in the chemotherapy industry towards the creation of new targeted drugs which are much more precise in their mechanisms of action. It is estimated that these targeted drugs will continue to take the place of conventional chemotherapy drugs in the future. This review describes the recent advances in cancer drug development in the United States in the past two decades.