Scientists Target Protein to Lower the Risk of Prostate Cancer Spread

According to a study conducted by Cedars-Sinai Cancer investigators, targeting a particular protein usually overexpressed in prostate cancer can assist stop or retard the disease from spreading to other body parts.

The study, published in the peer-reviewed journal Nature Communications, opens the possibility of using available commercial medications, including one approved by the Fda for leukemia, to shut down a protein known as receptor-interacting protein kinase 2- or RIPK2. The finding could significantly influence the treatment of men with advanced prostate cancer if confirmed in human clinical trials.

“Approximately 90% of cancer deaths are caused by the recurrence of metastatic cancer, which occurs when cancer spreads to other body organs,” stated Wei Yang, Ph.D. (associate professor of Surgery and Biomedical Sciences). “So, if we can stop the occurrence of metastatic cancer, we can significantly enhance the quality of life for men with this illness and prolong lives.”

To better comprehend the genetic drivers of sickness development and potential treatment targets, the Cedars-Sinai team analyzed in men with advanced prostate cancer, the molecular profiles of cancer tissue ductedThe investigators discovered that RIPK2 was amplified in approximately 65% of lethal prostate cancers, which kill approximately 34,000 U.S. men annually.

“The amplification of the protein RIPK2 was found increased together with cancer development, which revealed to us that this protein may have an essential function in cancer progression,” said Yiwu Yan, Ph.D., a first author of the study and a project scientist in the Yang Laboratory.

Yang said: ”while this protein has been examined in inflammatory illnesses, little is known about its molecular roles in the context of cancer development and metastasis.”

Once the protein was identified, the team ran a massive analysis to help decipher how RIPK2 might modify the activity of other functions in the cell. Investigators found that RIPK2 turns on another protein, which in turn causes an essential driver called c-Myc that fuels the development and metastasis of many cancer kinds, including prostate cancer.

In a sequence of experiments in mice, investigators discovered that inhibiting the RIPK2 function with both small molecular inhibitors (medicines) and a gene-editing system called CRISPR/Cas9 substantially decreased prostate cancer’s spread.

They discovered that targeting RIPK2 with ponatinib, an existing FDA-approved protein inhibitor, reduced prostate cancer metastasis by 92% in mice.

“Administrating RIPK2 tiny molecular inhibitors is a high-value method that decreased the metastasis in mice by over tenfold,” Wei Yang said. “If we can translate this to human patients, we may prolong patients’ lives by several years, rather than simply several months.”

Identification of biomarkers that can help investigators and clinicians choose the group of patients that would profit most from this treatment is the next step. Additionally, investigators will examine the results of RIPK2 inhibition on immune cells to see if the protein can potentially enhance the ability of immune cells to attack tumors.

“Targeting RIPK2 in preselected patients, either alone or in combination with emerging therapies or with standard, might hold the potential for improving the quality of life of cancer patients and the survival time,” Yang stated.

More information: Neuron (2021). DOI: 10.1016/j.neuron.2021.09.005

Read the original article on Medical Xpress.