MUSC Hollings Cancer Center Launches AUTOMAIN Trial Testing Repurposed Drugs for Recurrent Ovarian Cancer
核心洞察
MUSC Hollings Cancer Center (搜索) has launched the AUTOMAIN clinical trial for patients with recurrent ovarian cancer (搜索), testing repurposed drugs that target cellular autophagy (搜索) pathways.
The trial builds on over a decade of research showing that nearly all ovarian tumors have chromosomal abnormalities making them vulnerable to anti-autophagy drugs (搜索).
Up to 38 patients are expected to enroll in the study, which uses existing FDA-approved medications whose patents have expired, making them more affordable than newly developed treatments.
MUSC Hollings Cancer Center (搜索) has launched a new clinical trial for patients with recurrent ovarian cancer (搜索), marking the culmination of over a decade of collaborative research between basic scientists, physicians, and dedicated donors. The AUTOMAIN trial represents a novel approach to cancer treatment by repurposing existing drugs to target cellular autophagy (搜索) pathways in ovarian tumors.
Targeting Cellular Recycling Gone Wrong
The trial is built on groundbreaking research from Joe Delaney, Ph.D.'s laboratory, which discovered that nearly all ovarian tumors have chromosomal abnormalities that render them vulnerable to anti-autophagy drugs (搜索). Autophagy (搜索) is a cellular recycling process that, while protective in normal cells, ends up feeding tumors in advanced cancer.
"Starting from computers to see if the hypothesis makes sense, going into cells, trying out 32 different autophagy (搜索) drugs to see if any of them did anything, finally narrowing it down to the five that might actually be safe for patients and then trying that out in mice," Delaney explained, describing the research timeline that began in 2013 and continued through 2016. An additional four years of experiments were needed to ensure the drugs would be safe for use alongside chemotherapy.
Repurposing Existing Medications
A key feature of the AUTOMAIN trial is its use of drugs already approved for other diseases. This approach offers several advantages: investigators already understand the medications' side effects, typical dosages, and drug interactions. Additionally, because these drugs have been available long enough for their patents to expire, they are more affordable than newly developed treatments.
"This is an absolutely essential type of trial to perform with cancer patients, as many more drugs are expiring in patent protection each year," Delaney noted. However, the expired patent status creates a challenge, as pharmaceutical companies generally aren't interested in promoting new uses for drugs they no longer exclusively control.
Trial Design and Patient Enrollment
The FDA-approved trial expects to enroll up to 38 patients with recurrent ovarian cancer (搜索). Brian Orr, M.D., the physician lead and gynecologic oncologist, reports that the clinical team sees between six and 10 patients monthly who could potentially be eligible for the trial.
"These drugs are particularly effective at preventing chemotherapy-resistant cell populations from proliferating, in pre-clinical models," Delaney said. "We are optimistic that given the mechanism of action and the first-recurrence status of these patients, we have a strong likelihood to improve the survival of the women who enroll in this trial compared with current standard of care."
Building on Previous Success
This marks the second clinical trial to emerge from this research collaboration. The first trial, COAST, launched in 2022 under the clinical leadership of Michael Lilly, M.D. In that study, 14 patients with various cancers, including two with ovarian cancer (搜索), are using autophagy-inhibiting drugs (搜索). Many participants have maintained stable disease for months, according to Delaney, though final results won't be available for several years as the study continues.
Collaborative Funding Model
The trial represents a unique funding model, supported in part by donations raised by Matt Prisby, whose wife Sheryl Sirisky Prisby died of cervical cancer (搜索) in 2014. Prisby has raised more than $100,000 for gynecologic cancer research and emphasized the cost-effectiveness of the repurposed drug approach.
"Back in 2015, it was really hard to imagine that with so few dollars – in my mind – that we could do anything. It's a marvel to me. When you see research grants of millions and millions of dollars, and we've accomplished successful lab work – and now into trials," Prisby said.
The trial is also being funded by Hollings Cancer Center, which recognizes the significant potential of this research approach. Orr described the effort as "a true bench-to-bedside process," highlighting the successful translation of laboratory discoveries into patient care.