Researchers have found that a single enzyme called PI5P4Kα can be targeted to kill prostate cancer. The discovery is the first of its kind and could help tackle treatment resistance in prostate cancer. Additionally, it could lead to better treatment options for other types of cancer, including those affecting the breast, skin, and pancreas.
By inhibiting one enzyme, scientists from Sanford Burnham Prebys can kill prostate cancer cells when other treatments can’t.
For the first time, researchers have discovered that prostate cancer can be killed by targeting a single enzyme, called PI5P4Kα. The findings, published recently in the journal Science Advances<em>Science Advances</em> is a peer-reviewed, open-access scientific journal that is published by the American Association for the Advancement of Science (AAAS). It was launched in 2015 and covers a wide range of topics in the natural sciences, including biology, chemistry, earth and environmental sciences, materials science, and physics.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>Science Advances, could help address the growing threat of treatment resistance in prostate cancer and could also lead to improved treatments for other cancers, such as those affecting the breast, skin, and pancreas.
“This is the first time this enzyme has been implicated in prostate cancer, and we expect that it will prove relevant to other cancers as well,” says co-senior author Brooke Emerling, Ph.D., an associate professor at Sanford Burnham Prebys. “An important element of improving precision medicine is using as many tools as possible to treat cancer while mitigating the risk of resistance.”
Many cases of prostate cancer can be treated through treatments that lower testosterone and other male sex hormones, but about 10–20% of prostate cancer cases resist treatment within five years. This treatment-resistant prostate cancer can then spread to the rest of the body, where it becomes deadly.
“Understanding how prostate cancer develops resistance is critical for discovering new therapeutic strategies to delay or reverse the progression of prostate cancer,” says Emerling.
Brooke Emerling, Ph.D. Credit: Sanford Burnham Prebys
The prostate gland requires male sex hormones, known as androgens, to grow. Prostate cancer hijacks the androgen signaling machinery of the prostate in order to grow rapidly, which is why treatments that disrupt these pathways are effective.
“What’s remarkable is that we’ve found an enzyme that can be targeted against prostate cancer even in cases where treatments that lower hormones are ineffective or where resistance has developed,” says Emerling. “This could give us a whole new weapon against prostate cancer and other cancers that rely on this enzyme.”
The study was prompted by an observation made by Emerling’s colleagues at the University of BernFounded in 1834, the University of Bern (German: Universität Bern, French: Université de Berne, Latin: Universitas Bernensis) is located in the Swiss capital of Bern. It offers a broad choice of courses and programs in eight faculties and some 150 institutes.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>University of Bern, led by co-senior author Mark A. Rubin. They noticed that patients with treatment-resistant prostate cancer had high levels of PI5P4Kα, suggesting that this protein played a role in the cancer’s ability to resist treatment and grow. Emerling’s team was then able to show—using multiple prostate cancer model systems—that inhibiting this enzyme could kill treatment-resistant prostate cancer.
“It was that initial observation from the patient data that really got us excited,” adds Emerling.
PI5P4Kα is part of a group of enzymes called PI5P4Ks that are involved in the metabolism of lipids, a type of molecule that includes fats, hormones, and many vitamins. While other areas of cancer metabolism have been extensively researched for decades, lipid metabolism has only recently emerged as a promising therapeutic avenue for cancer.
“Treatments that target lipid metabolism could be an unexplored treasure trove, and it’s something researchers are very interested in right now,” says Emerling. “We’re working to develop drugs to target this enzyme, and there are several companies out there developing their own drugs as well.”
Because of this interest, Emerling and her colleagues are optimistic about the future of this treatment approach.
She says, “There’s no drug yet, but I have high hopes that in the near future, we’ll have something in clinical trials. That would be amazing.”
Reference: “PI5P4Kα supports prostate cancer metabolism and exposes a survival vulnerability during androgen receptor inhibition” by Joanna Triscott, Matthias Reist, Lukas Küng, Francielle C. Moselle, Marika Lehner, John Gallon, Archna Ravi, Gurpreet K. Arora, Simone de Brot, Mark Lundquist, Hector Gallart-Ayala, Julijana Ivanisevic, Salvatore Piscuoglio, Lewis C. Cantley, Brooke M. Emerling and Mark A. Rubin, 1 February 2023, Science Advances.
DOI: 10.1126/sciadv.ade8641
Additional authors of the study include Joanna Triscott, Matthias Reist , Lukas Küng , Francielle C. Moselle, Marika Lehner Simone de Brot, University of Bern; John Gallon and Salvatore Piscuoglio, University of Basel; Archna Ravi and Gurpreet K. Arora, Sanford Burnham Prebys; Mark Lundquist and Lewis C. Cantley, Weill Cornell Medicine; Hector Gallart-Ayala and Julijana Ivanisevic, University of Lausanne.
This study was supported by the Swiss National Science Foundation (SNF#31003A_175609 and SNF#310030_207635), an EU Commission Marie Skłodowska-Curie Individual Fellowship (PCAPIP), and The Johanna Dürmüller-Bol Foundation. Brooke Emerling was supported by NCI (R01 CA237536, CBC under contract 1053 no.75N91019D00024, task order no. 75N91020F00003) and ACS (RSG-20-064-01-TBE and TLC21-156-01). Lewis Cantley was supported by the National Cancer Institute (R35 CA197588). The metabolomics platform thanks SNF for the financial support: R’Equip grant no. 183377. Additional support was provided by the Englander Institute for Precision Medicine (EIPM).
Source: SciTechDaily
