Heavy lifting with HULLK
APIS, University of Virginia hope to leverage HULLK lncRNA as a prostate cancer biomarker
MANCHESTER, U.K. & CHARLOTTESVILLE, Va.—Nearly 20 percent of men will be diagnosed with prostate cancer, and many face relapse and a recurrence of their cancer. As with all cancer types, the earlier the disease can be detected, the better a patient’s chances are. And in hopes of providing a new diagnostic for such early detection, the University of Virginia and APIS Assay Technologies Ltd. are pursuing hormone-upregulated lncRNA within the lymphocyte-specific protein tyrosine kinase (HULLK).
Dr. Daniel Gioeli, an associate professor of microbiology, immunology and cancer biology at the University of Virginia, has demonstrated that HULLK can be detected in urine samples from prostate cancer patients, and he recently presented data regarding such detection at the 2020 Annual Meeting of the Society for Basic Urologic Research.
APIS and the University of Virginia began working together a year ago when they struck up a research agreement in December 2019 after APIS optioned the HULLK technology. The goal for this partnership is to evaluate the levels of HULLK in prostate cancer patients in order to determine guidelines for a clinical trial evaluating HULLK as a cancer biomarker.
“The latest data, which demonstrate the presence of this biomarker in non-invasive biofluids such as urine, is an exciting step forward,” stated Ian Kavanagh, chief operating officer of APIS Assay Technologies. “Our intention at APIS Assay Technologies is to implement HULLK into a clinically relevant signature for early detection of patients with metastatic prostate cancer and provide a guidance for further treatment.”
“There has been a lot of improvement in earlier detection of prostate cancer, but at the same time, it is still one of the major cancers in men; one in every five men in the world are affected by prostate cancer,” Dr. Joachim Schorr, CEO of APIS, tells DDN. “Some pathologists or doctors say it’s not a question of if you get prostate cancer, it’s a question of when, because it seems to be predetermined at a certain age that there’s tumor development. The challenge is not every prostate cancer is aggressive and fast-growing, so the major unmet need is a proper selection of tests to determine if you have an aggressive prostate cancer or a non-aggressive prostate cancer.”
Current diagnostic options often involve painful biopsies, and overtreatment can be an issue, especially given the side effects anti-androgen therapies can have on men. Given that, Schorr says, “There’s a need to have an easy, simple and very accurate detection where you can determine very early signs of aggressive prostate cancer, and this HULLK long non-coding RNA seems to be a marker indicating exactly that.”
HULLK is an unannotated lncRNA located within exon six and the 3’UTR of the LCK gene. This molecule is upregulated by androgen in a dose-dependent manner, an increase that can be blocked entirely by enzalutamide, a nonsteroidal anti-androgen medication for the treatment of prostate cancer (also known as Xtandi).
As reported by the University of Virginia in the 2019 press release of the discovery, HULLK levels are higher in patients with advanced prostate cancer, and decreasing HULLK levels in cultured prostate cancer cells slowed tumor growth. HULLK production is stimulated by androgen, and the researchers found that cells that overproduce HULLK were “hypersensitive” to androgen.
And the University of Virginia’s results regarding HULLK’s impact in prostate cancer are not a one-off; significant positive correlation between HULLK expression and high-grade prostate cancer has been seen in two other independent cohorts as well—one at the University of Texas Southwestern and one at The Cancer Genome Atlas.
Long non-coding RNAs (lncRNAs) represent the largest group of non-coding RNAs with approximately 55,000 genes. While components of the “dark genome” like non-coding RNAs have historically been ignored in favor of genes that code for proteins, research has shown that lncRNAs may play a role in regulating gene expression via interaction domains for DNA, messenger RNAs, micro RNAs and proteins, and lncRNA expression profiles can identify cancer subtypes that can offer insight into tumor behavior and disease prognosis.
“Overall, lncRNAs are emerging as critical regulatory elements of many cellular biological processes; that’s why APIS is also working with other lncRNA biomarkers in additional cancer-related indications,” Schorr commented in a press release.
“Our experience is in in-vitro diagnostics. What we aim to do is develop—and we are already now doing this—a PCR-based detection assay where you can detect HULLK out of urine as an early marker. But also there is the possibility to monitor treatment, how the level of HULLK is regulated by the treatment,” Schorr remarks. He notes that there is “more patient data coming” as they continue their work, and that they are aiming to have an assay with regulatory approval on a worldwide basis.
Schorr explains that APIS Assay’s approach is technology-agnostic, though PCR-based assays are among the most common. The company makes a point to “talk to the regulatory authorities very early on to understand what, from their perspective, is the need from the health provider,” he adds.
“This is really our approach: it’s to find the unmet need, to develop the appropriate assay and have the appropriate technology which meets the standard of clinical practice.”