Aiming To Cure More Cancer with PSMA Guided Fluorescence Robotic Prostatectomy
Despite advancements, prostate cancer cure rates remained stagnant over the last 20 yrs, with a 40% rate of postoperative positive surgical margins for patients with high risk disease. The challenge lies in distinguishing cancerous tissue during surgery. PSMA (prostate specific membrane antigen) based imaging, which highlights cancer cells by targeting a specific protein, offers a clearer view of the disease’s spread.
At UCSF, Dr. Carroll and I are pioneering the use of PSMA-targeted fluorescence in robotic prostatectomy. This approach allows us to detect and remove cancer as small as 2mm or in lymph nodes, which was previously undetectable. Our phase I study shows promising results, with 37.5% of high-risk patients benefiting from this technique. We’re moving towards larger trials, aiming for worldwide availability of this surgical innovation.
Publication:
Nguyen HG, van den Berg NS, Antaris AL, Xue L, Greenberg S, Rosenthal JW, Muchnik A, Klaassen A, Simko JP, Dutta S, Sorger JM, Munster P, Carroll PR. First-in-human Evaluation of a Prostate-specific Membrane Antigen-targeted Near-infrared Fluorescent Small Molecule for Fluorescence-based Identification of Prostate Cancer in Patients with High-risk Prostate Cancer Undergoing Robotic-assisted Prostatectomy. Eur Urol Oncol. 2024 Feb;7(1):63-72.
Investigating the Use of PSMA-Guided Ablation as a Focal Therapy
Traditional prostate cancer treatments often required surgery and radiation, but now we can now effectively manage and localize disease with noninvasive therapy directed at a single region, leaving the surrounding tissue intact. This includes high-intensity focused ultrasound (HIFU), in which precisely delivered ultrasound energy generates heat at a single point within the body to ablate (remove) selected tissue.
HIFU is approved by the US Food and Drug Administration (FDA) for ablation of prostate tissue, but while it potentially could provide better results than existing therapies, it is not approved explicitly for treating prostate cancer. Over the next year, I aim to develop a prospective study on post-HIFU tumor recurrence that integrates both imaging genomics and PSMA PET-guided ablation to decrease recurrence rates.
Pioneering Breakthroughs in Treating Metastatic Prostate Cancer
Prostate cancer remains a leading cause of death, and current treatments for advanced stages often fail. Our lab has discovered that proteins eIF4E and eIF4A, when overactive, drive prostate cancer growth. By targeting these proteins, we’ve seen significant tumor shrinkage in preclinical trials. I was awarded the 1 million PCF challenge grant to develop novel therapeutic strategies from the bases of these discoveries. Our progresses open the door to a new prostate cancer treatment called “translatome therapy,” which targets the process of protein creation in cancer cells. Unlike traditional treatments that focus on blocking cancer genes, this method aims at the proteins directly involved in cancer growth. We use a drug called Zotatifin, which is showing promise in early trials for stopping these proteins and slowing down the cancer. Our research suggests this could lead to better treatments for advanced prostate cancer, especially for patients who have tried other options without success.
In September, 2024 NIH SPORE grant will awarded to Drs. H. Nguyen, D. Ruggero and E. Small to continue this work in the next five years.
Publication:
Small molecule RNA therapeutics to target prostate cancer, in revision at Cancer Cell 2024. Nguyen and Ruggero (Co-Senior authors)