Research stage — aptamers and siRNA tested only in cells and animals; no proven effect in people Related drug trials: PI-88 phase III missed its primary goal; pixatimod phase Ib
A heparanase aptamer is a short piece of DNA (an aptamer) designed to bind heparanase (HPSE), an enzyme that helps cancer cells invade tissue and spread, and block its action. As of the date we checked the sources, blocking heparanase with aptamers or siRNA is still at the cell and animal research stage, and no benefit in people has been confirmed. PI-88, a drug that also inhibits heparanase, missed its primary goal in a phase III liver cancer trial, and pixatimod is in early (phase Ib) testing.
What is heparanase, and why study HPSE inhibition for cancer?
Outside our cells is a mesh of proteins and sugar chains (the extracellular matrix) and a thin layer around blood vessels (the basement membrane). Long sugar chains called heparan sulfate are abundant there and also store growth factors. Heparanase is the enzyme that cuts heparan sulfate; it is known as essentially the only enzyme in the human body that does this.
Laboratory studies have shown that when tumours make a lot of heparanase, this mesh loosens, making it easier for cancer cells to push into nearby tissue and blood vessels, and releasing stored signals that promote new blood vessel growth. This led researchers to ask whether blocking heparanase could reduce invasion, spread and blood vessel growth at the same time. The Japanese cancer information outlet GanMedi summarised this line of research in an explainer published in September 2026 and updated in October; this article checks the overseas papers it cites and re-explains them from a patient’s point of view.
There are three main approaches: (1) siRNA, a nucleic acid that destroys the gene’s messenger (mRNA) so less enzyme is made; (2) DNA aptamers, short DNA that binds the enzyme already made and blocks it; and (3) heparan sulfate mimetics (PI-88, pixatimod and others), drugs that imitate the enzyme’s target and trap it. The first two belong to nucleic acid medicine.
Which cancers were studied? Not treatment trials in patients
- Colorectal cancer: GanMedi cites an analysis of 130 surgical samples in which 5-year survival was 47.7% when heparanase was high and 84.6% when it was absent. This is an association only; it does not show that blocking heparanase extends survival.
- Gastric and breast cancer: cell and animal studies found that lowering heparanase with siRNA reduced invasion, movement and blood vessel formation.
- Ovarian and oral cancer: cell and tissue studies found that DNA aptamers reduced cancer cell invasion.
- Pancreatic cancer: in animals, adding a heparan sulfate mimetic to standard chemotherapy (such as gemcitabine) suppressed tumour growth more.
In other words, no patient has yet been treated in the aptamer or siRNA studies. Data from people exist only for heparan sulfate mimetic drugs, which also act on targets other than the enzyme.
Results by stage
| Approach / study | Model | Main result (as reported) | Stage |
|---|---|---|---|
| DNA aptamer (UK, PLoS ONE 2012) | Ovarian cancer cell invasion assay | At 1 µM for 24 h, invading cells fell from 74.4 (untreated) to 26.9; antibody 40.6 | Cell study |
| Short 30-base aptamer (PLoS ONE 2014) | Oral cancer tissue invasion model | Invasion inhibited; stable in human serum; effect attributed to enzyme inhibition, not general toxicity | Cell / tissue study |
| siRNA (BMC Cancer 2010 and others) | Gastric and breast cancer cells, animals | Less invasion, spread and blood vessel formation | Cell / animal study |
| PI-88 + gemcitabine + nab-paclitaxel (2026) | Pancreatic cancer animal models | Triple combination suppressed tumour growth and prolonged survival more than one or two drugs (as summarised by GanMedi) | Animal study |
| PI-88, PATRON phase III | Hepatitis-related liver cancer after surgery | 2014 interim analysis (131 events) did not meet the primary goal of improving disease-free survival | Human phase III |
| Pixatimod + nivolumab, phase Ib | 58 people, including microsatellite-stable (MSS) metastatic colorectal cancer | Among 25 evaluable MSS colorectal patients: response rate 12%, disease control rate 44% | Human phase Ib |
Sources: the individual papers and trial registrations. The table lists different studies side by side; their results cannot be compared directly.
Even the best-performing aptamer in the cell study was tested in only one cell line, and the authors wrote that animal studies are still needed. Results that look good in animals often fail to carry over to people. In fact, PI-88 did not meet its primary goal at the interim analysis of a phase III trial testing whether it reduces recurrence after liver cancer surgery.
In the early trial of pixatimod with the immunotherapy drug nivolumab, the maximum tolerated dose was set at 25 mg once a week. Of 58 participants, 12 (21%) had grade 3–5 treatment-related side effects, and one person at the 50 mg dose died of treatment-related multi-organ failure. The researchers explain that pixatimod’s effect is not due to heparanase inhibition alone but also to immune stimulation (via the TLR9 pathway). These results therefore cannot be used as evidence for aptamer treatment.
Approval status and self-pay care in Japan: where is it available?
- Approval: in the sources we checked, no cancer drug has been approved for the purpose of heparanase inhibition in the US, Europe or Japan. A 2019 journal review also noted that several candidates entered clinical trials but their development was discontinued or stalled.
- Clinical trials: human trials have mainly involved heparan sulfate mimetics (PI-88, pixatimod and others). We found no published clinical trial results for heparanase aptamers themselves in people.
- Self-pay care in Japan: GanMedi reports that some clinics in Japan offer DNA aptamer treatment aimed at heparanase as self-pay care (provided by the clinic outside public insurance and public approval), but that its effectiveness has not been established by large clinical trials.
Self-pay care is not illegal, but it also does not mean the treatment’s effectiveness and safety have been publicly verified. The full cost is paid by the patient and varies by clinic. The scope of the terms nucleic acid medicine and aptamer is explained in Nucleic acid medicine and aptamers: start by separating the terms, and related information on Japan is in our nucleic acid medicine and aptamer guide.
What to check and questions for your doctor
- What standard treatments and clinical trials are available for my cancer now?
- If I have been offered heparanase aptamer treatment, is there information on its ingredients, dose and manufacturing quality? Is there a published paper with results in people?
- Is it safe with the chemotherapy or immunotherapy I am receiving? Are there interaction or blood-clotting risks?
- How and when will we judge whether it works (scans, tumour markers)? When do we stop if it does not?
- What is the total cost and number of sessions, and which hospital will handle side effects?
Frequently asked questions
Does heparanase aptamer treatment work?
Cell and tissue studies showed reduced cancer cell invasion, but no clinical trial in people has confirmed a benefit. For now, the evidence remains at the laboratory stage.
Is there an approved HPSE inhibitor?
Not in the sources we checked. PI-88, which also inhibits heparanase, missed its primary goal in a phase III liver cancer trial, and pixatimod is at phase Ib.
How do aptamers differ from siRNA?
siRNA destroys the heparanase mRNA so less enzyme is made, while an aptamer binds directly to the enzyme protein already made and blocks it. Both are nucleic acid medicines but act at different points.
Can I receive heparanase aptamer treatment in Japan?
Some clinics reportedly offer it as self-pay care. It is not publicly approved or covered by insurance, so before starting, it is wise to get the supporting evidence, cost and how the clinic will coordinate with your main doctor in writing.
Related: Nucleic acid medicine and aptamers: start by separating the terms · Same name “photoimmunotherapy”, not the same treatment · NK cell therapy information
Sources
- Simmons SC, et al. Development of Novel Single-Stranded Nucleic Acid Aptamers against the Pro-Angiogenic and Metastatic Enzyme Heparanase (HPSE1). PLoS ONE 2012;7(6):e37938
pmc.ncbi.nlm.nih.gov/articles/PMC3376095
Checked on: 2026-10-16 - Anti-Heparanase Aptamers as Potential Diagnostic and Therapeutic Agents for Oral Cancer. PLoS ONE 2014
pmc.ncbi.nlm.nih.gov/articles/PMC4189786
Checked on: 2026-10-16 - Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells. BMC Cancer 2010;10:33
bmccancer.biomedcentral.com
Checked on: 2026-10-16 - Lemech C, et al. Phase Ib open-label, multicenter study of pixatimod, an activator of TLR9, in combination with nivolumab. J Immunother Cancer 2023;11:e006136 (NCT05061017)
pmc.ncbi.nlm.nih.gov/articles/PMC9843174
Checked on: 2026-10-16 - ClinicalTrials.gov — A Phase III PI-88 in the Adjuvant Treatment of Subjects With Hepatitis Virus Related HCC After Surgical Resection (NCT01402908)
clinicaltrials.gov/study/NCT01402908
Checked on: 2026-10-16 - BioCentury — PI-88 misses in interim analysis for hepatitis virus-related HCC (2014-08-08)
biocentury.com
Checked on: 2026-10-16 - Coombe DR, Gandhi NS. Heparanase: A Challenging Cancer Drug Target. Frontiers in Oncology 2019;9:1316
frontiersin.org
Checked on: 2026-10-16 - GanMedi — Why inhibiting heparanase (HPSE) is considered effective as cancer treatment (published 2026-09-27, updated 10-15; Japanese-language source)
ganmedi.jp/8660
Checked on: 2026-10-16
Written by the FTH editorial team. Sources checked 2026-10-16 · Medical review: not applicable
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your medical team.
