Development of Luminescent Small Molecules for Cancer Imaging and Therapy

On October 21, 2022, Dr. Sierra Marker King, a candidate for the biochemistry professor position at Amherst College, led this week’s Cheminar. She presented her doctoral and postdoctoral research. She began her higher education at SUNY Broome Community College and obtained an associate’s degree in Liberal Arts and Sciences. From there, she graduated from SUNY Binghamton with a Bachelor of Science in biochemistry. Afterwards, she acquired a master’s and doctorate in chemistry and chemical biology from Cornell University. Currently, she works at the National Cancer Institute as a postdoctoral researcher.

Dr. King began the presentation with a background to her doctoral research. She introduced the concept of platinum and the use of heavy metals to treat cancer. Cisplatin and carboplatin were extraordinary developments in the fight against cancer.  Discovered in 1965 by Dr. Barnett Rosenburg, these drugs target DNA and stop cell reproduction. Dr. King said that 50% of cancer therapies are now platinum-based drugs. From there, research began on other heavy metal-based treatments. Dr. King’s doctoral research centered on rhenium complexes as therapeutic agents. Specifically, she focused on tricarbonyl rhenium isonitrile polypyridyl (TRIP).

TRIP Molecule 

Source: https://www.mdpi.com/1420-3049/25/18/4176/htm

The advantages of the TRIP molecule are that it has high solution stability, aqueous solubility, and phosphorescence. This molecule also has comparable or better cytotoxicity than cisplatin. TRIP eliminates cancer cells by activating the unfolded protein response pathway and causing mitochondrial dysfunction. First, TRIP binds to the NUBP2 protein. Then, it causes mitochondrial dysfunction. After, it causes protein aggregation and endoplasmic reticulum (ER) stress. Finally, these factors cause apoptosis – a programmed form of cell death.

Dr. King then moved on to her post-doctoral work. She introduced new cancer therapeutics called antibody-drug conjugates. She displayed Mylotarg as an example, which was used to treat leukemia but has since been withdrawn over concerns about toxicity. Dr. King discussed her research into fluorophores detecting tumors. In the future, Dr. King wants to research using fluorophores to evaluate tyrosinase levels to detect melanoma. She is driven to start research on darker skin since most melanoma research was historically conducted on white/non-Hispanic skin.

Overall, Dr. King had a compelling lecture. Her research has the potential to save many lives. I believe she could become a great professor at Amherst. With Amherst’s resources, she will be able to continue this research and have the opportunity to evolve cancer treatments.