Characterization of A Novel Oncogenic Mirna Inhibitor In Cancer Therapy

<p>As cancer research continues to move towards more personalized methods, targeted inhibitors of oncogenic drivers of cancer are found to be an innovative and promising therapeutic approach. Previously thought to be undruggable regions of the genome, RNA has become an area of increasing interest in cancer due to the identification of more targetable regions and their relationship to tumor growth and progression. This work reports on the development of IACS-13743, a novel small molecule found to directly bind and inhibit microRNA-10b. Oncogenic miR-10b has been found to be overexpressed in several malignant cancer types, making it an attractive biomarker for targeted inhibitor therapy. IACS-13743 is found to impede tumor progression and proliferation in brain cancer, gastric cancer and pancreatic cancer <em>in vitro</em>. This effect is also shown in a cerebral organoid model. Using a multidisciplinary approach, this study identifies a relationship between oncogenic miR-10b and the dysregulation of the PI3K/AKT pathway in cancer, along with putting forth a compound that can mitigate these effects. These findings provide a fundamental step in moving forward a targeted therapeutic for a known oncogenic RNA driver and unique biomarker in multiple malignant cancer types.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2021

Author dc:creator

• Sahnoune, Iman

Contributors dc:contributor

• George Calin, MD, PhD
• Pratip Bhattacharya, PhD
• Giulio Draetta, MD, PhD

• RNA therapeutics
• drug discovery
• small molecules
• cerebral organoids
• Medicine and Health Sciences
• Neuroscience and Neurobiology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1105

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2160