Attacking a protein in prostate cancer cells stops the disease spread, research finds

Cedars-Sinai scientists discovered that attacking a protein present in prostate cancer cells could stop the disease from further spreading to various other parts of the body in mice.

Attacking a protein in prostate cancer cells stops the disease spread, research finds
New research from Cedars-Sinai Cancer targets a specific protein to prevent or delay the spread of prostate cancer, symbolized by the blue ribbon. Image Credit: Getty

According to a study headed by Cedars-Sinai Cancer investigators, attacking a certain protein that is usually overexpressed in prostate cancer can aid in preventing or delaying the disease from spreading to various other parts of the body.

The research opens the potential of employing available commercial drugs, alongside the one approved by the Food and Drug Administration for leukemia, to target a protein known as receptor-interacting protein kinase 2—or RIPK2. If proved in human clinical trials, the result can have a great influence on the treatment of patients with advanced prostate cancer. The study was published in the peer-reviewed journal Nature Communications.

About 90% of cancer deaths are caused by the recurrence of metastatic cancer, which occurs when cancer spreads to other organs. So, if we can prevent the occurrence of metastatic cancer, we can substantially extend the lives and improve the quality of life for men with this disease.”

Wei Yang, PhD, Associate Professor, Surgery and Biomedical Sciences, Cedars-Sinai Medical Center

To better comprehend the genetic influencers of disease development and probable treatment targets, the Cedars-Sinai team analyzed the molecular profiles of cancer tissue in patients with advanced prostate cancer. The investigators found that RIPK2 was amplified in around 65% of lethal prostate cancers that kill about 34,000 US men every year.

We found the amplification of the protein RIPK2 increased along with cancer progression, which showed us that this protein may have a very important role in cancer progression.

Yiwu Yan PhD, First Author and Project Scientist, Yang Laboratory

Although this protein has been explored in inflammatory diseases, there is very little knowledge about its molecular functions concerning cancer progression and metastasis, Yang said.

Once the protein was found, the team performed a large-scale analysis to aid decode how RIPK2 may change the activity of other cell functions. Investigators discovered that RIPK2 stimulates another protein, which in turn activates a critical driver known as c-Myc that drives the progression and metastasis of several cancer kinds, including prostate cancer.

In a range of experiments conducted in mice, investigators discovered that inhibiting the RIPK2 function with both tiny molecular inhibitors (drugs) and a gene-editing system—known as CRISPR/Cas9—considerably decreased the spread of prostate cancer.

They discovered that attacking RIPK2 with ponatinib, an already-present FDA-approved protein inhibitor, decreased prostate cancer metastasis in mice by 92%.

Administrating RIPK2 small molecular inhibitors is a high-value strategy that reduced the metastasis in mice by over tenfold. If we can translate this to human patients, we may extend patients’ lives by several years, instead of just several months.”

Wei Yang PhD, Associate Professor, Surgery and Biomedical Sciences, Cedars-Sinai Medical Center

The next step is to find biomarkers that can aid in guiding investigators and clinicians to choose the group of patients that will benefit most from this therapy. Also, investigators will assess the effects of RIPK2 inhibition on immune cells to check whether the protein can enhance immune cells’ capacity to target tumors.

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

Source:
Journal reference:

Yan, Y., et al. (2022) Receptor-interacting protein kinase 2 (RIPK2) stabilizes c-Myc and is a therapeutic target in prostate cancer metastasis. Nature Communications. doi.org/10.1038/s41467-022-28340-6.

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