Samantha Yee is the first author on this two-author publication from Dr. April L. Risinger’s lab. She currently has three first author (2 research articles and 1 review) and three co-author publications.
The paper, “Efficacy of a Covalent Microtubule Stabilizer in Taxane-Resistant Ovarian Cancer Models,” was published on July 3rd, 2021 in Molecules in the Special Issue Natural Products in Cancer Research: From Isolation to Mechanisms of Action.
“Ovarian cancer research has always been an interest of mine,” Yee said. “Women’s health matters and I am humbled to have the opportunity to conduct women’s cancer research.”
According to Cancer Statistics, 2020 which is cited in the paper, around 22,000 women are diagnosed with ovarian cancer in the United States of which 14,000 will succumb to the disease.
Yee explained that ovarian cancer is a heterogeneous disease that has few targeted therapies and high rates of metastasis. Further, ovarian cancer patients have a poor prognosis as they are often diagnosed at late stages after localized peritoneal metastasis has occurred.
“The standard of care for ovarian cancer is a combination chemotherapy consisting of a taxane microtubule stabilizer and platinum-based agent,” she said. “Unfortunately, up to 70 percent of ovarian cancer patients acquire resistance to taxane-based chemotherapy within 18 months of treatment. Therefore, it is essential to identify new strategies and therapeutics for the treatment of metastatic, drug-resistant disease.”
In this study, the researchers demonstrated that a covalent microtubule stabilizer derived from plants, taccalonolide AF, retains efficacy against drug-resistant ovarian cancer models. Specifically, they found that taccalonolide AF was efficacious in vivo against a taxane-resistant ovarian cancer model both as a flank xenograft as well as in a disseminated model of localized metastasis. In the mouse model representing localized metastasis, they found that taccalonolide AF significantly reduced micrometastasis to the spleen compared to the standard of care, paclitaxel, a taxane microtubule stabilizer.
“The findings demonstrate that taccalonolide AF retains efficacy in taxane-resistant ovarian cancer models in vitro and in vivo and that its covalent and irreversible mechanism of microtubule stabilization has the unique potential for intraperitoneal treatment of locally disseminated taxane-resistant disease, which represents a significant unmet clinical need in the treatment of ovarian cancer patients,” she said.
Yee explained that the next steps for this project would be the clinical development of covalent microtubule stabilizers for cancer treatment including tumor targeting strategies to decrease systemic toxicity and improve the therapeutic index.