Cancer drugs patient survival pre-clinical clinical cost

Cancer drug development: The missing links

by Ajaikumar B Kunnumakkara kunnumakkara@iitg.ac.in, Devivasha Bordoloi, Bethsebie Lalduhsaki Sailo, Nand Kishor Roy, Krishan Kumar Thakur, Kishore Banik, Mehdi Shakibaei, Subash C Gupta, and Bharat B Aggarwal

Apr 18^th 2019
20 mins
Experimental Biology and Medicine 2019; 244: 663–689.

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Summary

Despite advanced science and technology, cancer incidence is highest in America and Europe.
Science and technology alone are not sufficient for treating diseases like cancer.
Over 95% of drugs/compounds that show promise in pre-clinical trials fail in phase I clinical trials in humans.
Most pre-clinical models of cancer are inadequate.
Many FDA-approved anticancer drugs have little to no effect on overall survival or only offer a marginal increase in survival.
Targeted therapies are often highly expensive and lack affordability.
Cancers are caused by multiple genes, necessitating multi-targeted therapies.
Natural products, which are inexpensive, safe, and used for thousands of years, are suggested as potential multi-targeted therapies for cancer.

Cancer is a group of more than 200 neoplastic diseases, caused by diverse deregulated cell signaling cascades. It represents the leading causes of morbidity as well as mortality across the globe and over the coming two decades, its incidence is predicted to increase by approximately 70% Among all the cancers, lung cancer is reported to be most commonly diagnosed one followed by female breast cancer, prostate cancer, and colorectal cancer. Notably, lung cancer also represents the most common cause of death due to cancer followed by colorectal cancer, stomach cancer, and liver cancer. Further, lung cancer is the most common cancer and the leading cause of cancer death among males, whereas breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among females.

Consumption of tobacco and alcohol, obesity, insufficient physical activity, exposure to ultraviolet radiation, and various dietary factors which include insufficient fruit, non-starchy vegetables, and fiber; red/processed meat are predicted to be strongly associated with the risk of diverse cancer t ypes. Cancer occurs as a result of the dysregulation of as many as 500 different genes which may happen over a very long duration of time (20–30 years) till the symptoms become apparent. Large-scale sequencing of human cancer genome has revealed 1007 somatic mutations in 274 megabases of DNA which corresponds to the coding exons of 518 protein kinase genes in 210 different human cancers comprising of 169 primary tumors, two early cultures, and 39 immortal cancer cell lines. The majority of the somatic mutations are predicted to be ‘‘passengers’’ with no role in the development of cancer, whereas “driver” mutations were well evinced to play role in oncogenesis.

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Cancer, drugs, patient survival, pre-clinical, clinical, cost