Prostate cancer is the second-leading cause of cancer death among men in the United States; about 33,330 men are expected to die of the disease this year.
Most prostate cancers remain confined to the prostate and can be successfully managed by active surveillance or local therapy, with five-year survival rates above 99%. But once prostate cancer spreads, it is considered incurable, and five-year survival rates drop to approximately 30%.
To identify a more accurate method of predicting advanced prostate cancer, the researchers first created a mouse model of prostate cancer that accurately reflects the human form of the disease, including how the cancer spreads to the bone, the tissue most often affected by prostate cancer metastases.
The researchers discovered that bone metastases have a different molecular profile than that of primary tumors. “By focusing on those differences, we were able to identify 16 genes that drive localized prostate cancer to metastasize,” Abate-Shen says.
The genetic signature, called META-16, was then tested on biopsies from several hundred patients with localized prostate cancer. META-16 was highly effective at predicting time to metastasis and response to anti-androgen therapy.
In theory, META-16 could also be used to develop therapies against metastatic prostate cancer.
“The genes in our signature are not only correlated with metastasis, they appear to be driving metastasis,” Arriaga says. “That means that if we can suppress the activity of those genes, we might be able to prevent the cancer from spreading or at least improve outcomes.”
Juan M. Arriaga, Sukanya Panja, Mohammed Alshalalfa, Junfei Zhao, Min Zou, Arianna Giacobbe, Chioma J. Madubata, Jaime Yeji Kim, Antonio Rodriguez, Ilsa Coleman, Renu K. Virk, Hanina Hibshoosh, Onur Ertunc, Büşra Ozbek, Julia Fountain, R. Jeffrey Karnes, Jun Luo, Emmanuel S. Antonarakis, Peter S. Nelson, Felix Y. Feng, Mark A. Rubin, Angelo M. De Marzo, Raul Rabadan, Peter A. Sims, Antonina Mitrofanova, Cory Abate-Shen. A MYC and RAS co-activation signature in localized prostate cancer drives bone metastasis and castration resistance. Nature Cancer, 2020; DOI: 10.1038/s43018-020-00125-0
Columbia University Irving Medical Center. “Gene signature predicts whether localized prostate cancer is likely to spread.” ScienceDaily. ScienceDaily, 10 November 2020. <www.sciencedaily.com/releases/2020/11/201110154304.htm>.
Photo by Misael Moreno