Chemistry Professor Contributes to a Cancer Treatment Now in Clinical Trials

Max Royzen, second from right, worked with his lab team and biotech firm Shasqi to develop a chemical compound used in a cancer treatment currently in clinical trials. (Photo by Brian Busher)

ALBANY, N.Y. (Nov. 19, 2020) – A cancer therapy that uses a chemical compound developed with the help of a UAlbany scientist has entered a Phase I clinical trial for treating patients with advanced solid tumors.

Max Royzen, an associate professor of Chemistry, partnered with San Francisco-based biotech firm Shasqi to develop an anticancer therapy that utilizes bio-orthogonal click chemistry to target a powerful drug at cancerous tumors. Bio-orthogonal click chemistry is a process by which two highly reactive compounds, selective for each other, react inside a live organism. According to Royzen, this makes the process incredibly valuable in medicinal chemistry and in particular cancer treatment, because it can target the cancerous cells while sparing healthy cells.

Royzen and a postdoctoral scientist, Kui Wu, have been collaborating with Shasqi for many years to develop a drug delivery platform using one of the fastest bio-orthogonal click reactions, a Diels-Alder cycloaddition between tetrazine and trans-cyclooctene (TCO). The therapy involves two main components. The first involves modifying a sodium hyaluronate biopolymer to include tetrazine groups (which is later injected into the patient). The second component uses a protodrug of doxorubicin (a popular chemotherapy medication used in the treatment of breast cancer, bladder cancer, certain types of sarcoma, lymphoma and leukemia), modified with TCO. Conventional doxorubicin, while often effective, can cause severe side effects including cardiotoxicity.

In the clinical trials, a patient is first given an injection of the sodium hyaluronate biopolymer. Patients then receive five daily infusions of TCO-modified doxorubicin, which circulates the drug through the body until it finds the sodium hyaluronate biopolymer and a click reaction occurs to bring the biopolymer and doxorubicin together. This reaction triggers the doxorubicin to touch only the tumor cells while leaving the healthy surrounding cells intact.

According to Royzen and the Shasqi team, the TCO-modified doxorubicin appears to be 80 times less toxic than conventional doxorubicin. The researchers say that in addition to reducing side effects, this method could also greatly increase the amount of doxorubicin that a patient is able to safely tolerate.

“All of us in the Royzen Lab are really excited to be a part of this process, as few compounds developed in academic labs get a chance to be tested in human clinical trials,” said Royzen, who is also an affiliate faculty member at the RNA Institute.

Preclinical results of the platform technology are currently undergoing peer-review and are expected to be published in 2021.

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