Cancer drug development: The missing links

Abstract

Although better science and technology has been linked with better health care, however, reality is much different. Although America and most of Europe are equipped with most advanced science and technology, paradoxically cancer incidence is highest in the world. This indicates that science and technology alone is not sufficient in treating diseases like cancer. It is also now well recognized that more than 95% of the drugs/compounds that kill either cancer cells in culture or regress the tumors in animals, fail in phase I clinical trials in humans, indicating that most pre-clinical models of cancer are inadequate. In addition, most of the anticancer drugs that are approved by the regulatory agencies such as FDA either has no effect on the overall survival of the cancer patient or may provide an increase in few months in overall survival. This is despite the fact that most targeted therapies that are currently available are highly expensive; thus suggesting the lack of affordability. This review is meant to focus on some of these problems in detail and then provide potential solutions since most cancers are caused by multiple genes, and thus multi-targeted therapies are needed such as natural products which are inexpensive, safe and have been used for thousands of years for both prevention and treatment of cancer. Impact statement The success rate for cancer drugs which enter into phase 1 clinical trials is utterly less. Why the vast majority of drugs fail is not understood but suggests that pre-clinical studies are not adequate for human diseases. In 1975, as per the Tufts Center for the Study of Drug Development, pharmaceutical industries expended 100 million dollars for research and development of the average FDA approved drug. By 2005, this figure had more than quadrupled, to $1.3 billion. In order to recover their high and risky investment cost, pharmaceutical companies charge more for their products. However, there exists no correlation between drug development cost and actual sale of the drug. This high drug development cost could be due to the reason that all patients might not respond to the drug. Hence, a given drug has to be tested in large number of patients to show drug benefits and obtain significant results.

Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties

“…With the discovery of induction routes of cancer, the race to identify a cure has accelerated [90]. To translate phytochemicals into clinical setting, the efficiency of the drugs needs to be improved through enhancing the drug interactions, drug dynamics, and other pharmacokinetic parameters [193]. Although the biological effect of Rheum rhizomes in several polyherbal extracts are of high ethnopharmacological importance, there are fewer data available from pharmacokinetic studies of rhein alone.…”

An Update on Pharmacological Potential of Boswellic Acids against Chronic Diseases

“…In the year 2012, it was estimated that about 14.1 million people suffered from the disease and 8.2 million people succumbed to death, whereas in the year 2018, the number of deaths increased to 9.8 million worldwide [162,163,164,165,166]. Notably, the majority of the existing drugs exert severe side effects and are mostly ineffective due to the development of chemoresistance [23,167,168,169]. This has led to shifting of attention towards natural products such as butein, emodin, curcumin, epigallocatechin gallate (EGCG), celastrol, honokiol, resveratrol, etc.…”

Natural Products and Synthetic Analogs as a Source of Antitumor Drugs

“…Unfortunately, most of the anticancer FDA-approved drugs and other regulatory agencies have no effect on the overall survival of the cancer patient. Cancer cell lines and animal models are a valuable tool for cancer research but reports indicate that these preclinical models are highly incomplete and not match with results obtained from clinical studies [297]. Finding a way to design drugs that effectively hit the mark is a major challenge.…”