Review spotlights FL118 and dual cancer target degradation: full analysis
A new review is making the case that DDX5 and UbE2T deserve closer attention as cancer drug targets, especially in hard-to-treat solid tumors, and it puts FL118 at the center of that story. In the Journal of Experimental & Clinical Cancer Research, the authors describe the first comprehensive review focused on the physical and functional relationship between DDX5 and UbE2T, arguing that simultaneous degradation of both proteins by FL118 could open a new therapeutic strategy for resistant cancers. (pubmed.ncbi.nlm.nih.gov)
That argument builds on several years of work around FL118. Roswell Park researchers reported in 2022 that FL118 directly binds to DDX5 and promotes its degradation through the proteasome pathway, positioning the compound as a molecular glue degrader rather than simply a conventional cytotoxic agent. Subsequent publications and reviews have continued to describe FL118 as a DDX5-targeting anticancer candidate with activity in pancreatic, colorectal, and other tumor models, while a separate body of literature has highlighted UbE2T as an emerging cancer-related ubiquitin-conjugating enzyme with broad relevance across tumor types. (roswellpark.org)
The new review appears to be more about synthesis and positioning than about reporting a new clinical data set. Its central claim is that DDX5 and UbE2T are mechanistically linked and may be better attacked together than separately, with FL118 presented as a candidate capable of dual molecular glue target degradation. That matters because both proteins have been implicated in tumor growth, metastasis, and treatment resistance, but neither has been an easy target for traditional drug development. More broadly, the paper lands at a moment when molecular glues are getting renewed attention as a way to drug proteins that have historically been considered difficult or “undruggable.” (mdpi.com)
There are also signs that the FL118 program is advancing beyond theory. ClinicalTrials.gov lists an ongoing Phase 1 study of FL118 in patients with advanced pancreatic ductal adenocarcinoma, with Roswell Park as sponsor and a record update posted January 17, 2025. Roswell Park also announced in January 2024 that FL118 received FDA orphan drug designation for pancreatic cancer. In parallel, an NCI SBIR investor initiative document described planned milestones that included an IND filing in 2025 and Phase 1 development in 2025 to 2026, suggesting an active commercialization pathway around the asset. (clinicaltrials.gov)
Outside commentary specific to this new review was limited in the sources available, but the surrounding literature points to both promise and caution. Reviews of DDX5 describe it as a multifunctional RNA helicase involved in transcription, RNA processing, and oncogenic signaling, while UbE2T reviews note broad cancer associations but also emphasize that much of the evidence remains preclinical. That’s an important distinction: the biological rationale is expanding, but the translational and clinical proof is still catching up. (sciencedirect.com)
Why it matters: For veterinary professionals, this is mainly a translational oncology signal rather than a practice-changing development. There’s no direct veterinary indication here, and no evidence yet that FL118 is ready for animal cancer care outside research settings. Still, the story is relevant for comparative oncology because it reflects a broader shift toward targeted protein degradation, rational multi-target strategies, and biomarker-driven development in cancers that remain difficult to treat in both people and animals. Veterinary oncologists at referral centers and research institutions may especially want to watch whether DDX5- or UbE2T-linked biology shows up in canine or feline tumor research, and whether molecular glue approaches start to move into comparative studies. That last point is an inference based on the direction of the field, not a claim from the paper itself. (mdpi.com)
What to watch: The next meaningful test will be clinical, not conceptual: dose-escalation and safety findings from the ongoing pancreatic cancer trial, followed by evidence that FL118’s proposed dual-target degradation mechanism can be confirmed in patients and tied to outcomes. If those data emerge, the conversation could shift from an intriguing review thesis to a more actionable oncology platform. (clinicaltrials.gov)