Northwestern Medicine researchers have uncovered the Achilles heel of chemotherapy-resistant ovarian cancer – its need for cholesterol — and how to utilize it to get rid of it.
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In a recent study, researchers discovered that chemotherapy-resistant ovarian cancer cells and tumors are high in cholesterol due to enhanced absorption. They then used a synthetic nanoparticle that the cancer cells mistook for a natural cholesterol-rich one.
However, when the cancer cells linked to the fake particle, the mimic actually inhibited cholesterol absorption. Furthermore, the researchers demonstrated that lowering cholesterol fooled cancer cells into a cell death pathway. The nanoparticle treatment suppressed ovarian tumor development by more than 50% in human cells and animal models.
This is a new weapon to destroy resistant ovarian cancer.
C. Shad Thaxton, Associate Professor of Urology, Feinberg School of Medicine, Northwestern University
Study co-corresponding author Dr. Daniela Matei, a professor of medicine at Northwestern University Feinberg School of Medicine and a Northwestern Medicine oncologist, stated, “More than 18,000 women die of ovarian cancer every year. Finding new ways to attack resistant cancer cells is very important.”
Matei and Thaxton demonstrate that cell death following treatment with these nanoparticles is caused by the oxidation of lipids in the cell membrane.
Dr. Matei added, “These cancer cells are resistant to the typical form of death — apoptosis — which is why chemo can’t kill them.”
Thaxton and Dr. Leo Gordon’s previous pre-clinical research employing nanoparticles to treat lymphoma was expanded upon in the ovarian cancer study.
This latest study, published recently in Advanced Science, demonstrated that the method also works in ovarian cancer cells.
Matei and Thaxton examined the nanoparticles in xenografts of chemotherapy-resistant ovarian cancer in animals as well as in ovarian cancer cells. The next phase of the investigation will involve comparing the combination of the particles with conventional chemotherapy and examining how the nanoparticles affect immune cells that combat cancer.
Matei also serves as the Diana Princess of Wales Professor of Cancer Research. She and Thaxton are members of Northwestern University's Robert H. Lurie Comprehensive Cancer Center.
Yinu Wang; Andrea E. Calvert; Horacio Cardenas; Jonathon S. Rink; Dominik Nahotko; Wenan Qiang; C. Estelle Ndukwe; Fukai Chen; Russell Keathley; Yaqi Zhang; and Ji-Xin Cheng are the other Northwestern authors.
Nanoparticle Targeting in Chemo-Resistant Ovarian Cancer Reveals Dual Axis of Therapeutic Vulnerability Involving Cholesterol Uptake and Cell Redox Balance is the name of the study.
The study was supported by a grant from the US Department of Defense Office of the Assistant Secretary of Defense for Health Affairs’ Ovarian Cancer Research Program.
Journal Reference:
Wang, Y., et. al. (2024) Nanoparticle Targeting in Chemo-Resistant Ovarian Cancer Reveals Dual Axis of Therapeutic Vulnerability Involving Cholesterol Uptake and Cell Redox Balance. ACS Nano. doi:10.1002/advs.202305212.
Source: https://www.northwestern.edu/