Engineer Primary Cilium via Pharmacological Inhibition of CILK-1 to Modulate Signaling; Investigating Hurdles with the Extensive Duration of FDA Approval Process for New Oncogenic Therapeutics

Wang, Elena, School of Engineering and Applied Science, University of Virginia
JACQUES, RICHARD, EN-Engineering and Society, University of Virginia
Fu, Zheng, MD-PHAR Pharmacology, University of Virginia

For decades, cancer has been a significant issue concerning the entire human race. Being the leading cause of death after cardiovascular diseases, it has impacted billions of families and the society in general in the U.S. and worldwide. It is predicted that in the year of 2022, there will be an estimated 1.9 million new cancer cases diagnosed and 609,360 cancer deaths.1 Extensive amount of time and money is put into research and development of new oncogenic drugs every year due to the hurdles in cancer treatments impacting society in the past centuries. Despite the effort, the nature of tumor cells allow them to develop resistance towards these discovered therapies, making treatments no longer effective and wasting the resources and time spent along the drug discovery and approval process. The question thus arises: how can cancer drug resistance be prevented to save numerous existing and new therapies?
Primary cilium, a microtubule-based structure in cells, is known as the cellular antenna because of its critical roles in transducing environmental signals to regulate cell signaling pathways, many (e.g. Hedgehog and Wnt pathways) are related to the development of drug resistance of various cancer cells. Study has shown that modulation of primary cilium length helps regain cancer drug sensitivity.2 The technical project focuses on engineering the cilia dynamic structure, more specifically its length, via the use of drug molecule Alvocidib and its inhibition of protein kinase Ciliogenesis Associated Kinase 1 (CILK1).
All drug molecules, however, require approval from the Food and Drug Administration (FDA), and the extensive process before licensing is inevitable despite the time-sensitive nature of oncogenic drugs. What role does the FDA play in ensuring the new cancer therapies get to vulnerable patients in a timely manner? Since 2012, the accelerated approval process has allowed the FDA to base approval of drugs for serious conditions, and such a process has been mainly used for oncology drugs.3 However, many limitations exist within the system, and the risk-benefit between strictly ensuring the safety of new drugs developed versus the time sacrificed in getting them to more patients remains a baffling dilemma.

BS (Bachelor of Science)
FDA, Primary Cilium, Drug Approval

School of Engineering and Applied Science
Bachelor of Science in Biomedical Engineering
Technical Advisor: Zheng Fu
STS Advisor: Richard Jacques

Issued Date: