HELIONEX
Here for CDH1
Estimated 80 pathogenic germline carriers per
one million people
20-30 – Generally the recommended age range for preventative total gastrectomy even if asymptomatic ‡
Precision oncology therapies to safely and permanently restore essential E-cadherin function
What is CDH1?
Precision technologies now enable FDA-approved, gene-based therapies for serious inherited diseases.2 We aim to design and test a targeted gene-based therapeutic for individuals with pathogenic germline CDH1 variants. The goal of the CDH1 precision cancer therapeutic is to significantly improve quality of care by expanding the precision cancer treatment options for CDH1-variant asymptomatic carriers and cancer patients with CDH1-gene mutations that prevent the production of a critical protein.
CDH1 is a gene that encodes E-cadherin, a protein that provides critical roles in the human body.3,4 Vital organs including the stomach contain epithelial cells, which rely on E-cadherin to bind the cells for normal tissue structure.5 Inside a healthy epithelial cell, E-cadherin also recruits β-catenin, an important proto-oncogene transcription activator, which reduces the expression of genes that promote cancer proliferation and survival (Figure right).5,6,14 CDH1 is a tumor suppressor gene whose loss-of-function is clinically significant.
Cancer onset and development
As mentioned, defective or deficient E-cadherin impairs normal cell-to-cell adhesion, which promotes cell displacement.7 Cancer develops when the displaced epithelial cells divide in the wrong location. Evasively, the microscopic nature of these early-stage cancer cells is often undetected in biopsies and endoscopies.1 For example, 66% (4/6) of pathogenic CDH1-variant carriers with negative endoscopies, who chose gastrectomy, had cancer in their resections.8 Specialized endoscopic teams experience the challenges.9 Support organisations provide outstanding services.†
Germline CDH1 pathogenicity is related to specific cancer types: Hereditary Diffuse Gastric and Lobular Breast Cancers (HDGC).10,11 Carrier lifetime cancer risk depends on the cancer type and study. For example, Ryan et al. (2024) estimated the breast cancer likelihood for female carriers was 37% (95% CI, 25.7%-62.9%).12 The known high risk of cancer and 50% chance of passing the pathogenic variant on has wider implications. A 2025 study found complex dependencies relating to carrier family planning.13
Given the limitations of current clinical management—which principally relies on irreversible surgery or observation with risk—there is a pressing need for precise non-invasive, durable alternatives. Helionex seeks to join experts in CDH1 and gene editing to develop a nucleic-acid-based therapeutic to permanently rescue the CDH1 wild-type sequence, restore normal E-cadherin expression, and reestablish CDH1‘s tumor-suppressor function.3 In collaboration with leading biomedical institutions, this approach will be evidenced through rigorous preclinical testing in cell and humanized models. Should these studies demonstrate safety and signal efficacy, we will initiate clinical development in partnership with pharmaceutical industry leaders. To date, no available therapy provides durable restoration of the CDH1 gene—an unmet need we intend to address.5,15–25
Partner with Us
Helionex welcomes partnerships with biomedical researchers, pharmaceutical developers, and investors interested in advancing gene-based precision therapies to prevent CDH1-related cancers. If your organization shares our vision of transforming preventive care for cancer, we invite you to contact us to explore collaborative opportunities.
Helionex
Our Values
At Helionex, we believe:
That a small act is worth doing if it can lead to a lasting, positive impact.
That steady progress outperforms speed when the road is steep.
That growth and science should always be net positive — for people and for the planet.
That collaboration creates enduring value beyond what competition alone can achieve.
And that the future of care should be precise, preventive, and personal.
Reference Title Links.
‡ Hereditary Diffuse Gastric Cancer: Updated Clinical Practice Guidelines
† Hereditary Diffuse Gastric Cancer: HDGC advocacy.
- CDH1 (E-cadherin) mutation and gastric cancer: Genetics, molecular mechanisms and guidelines for management.
- FDA approves first gene therapies to treat patients with sickle cell disease.
- MedlinePlus CDH1 gene.
- Gene of the month: E-cadherin (CDH1).
- Overview on the role of E-cadherin in gastric cancer: Dysregulation and clinical implications.
- Hereditary Diffuse Gastric Cancer (PDQ®)–Health Professional Version.
- Therapeutic and prophylactic gastrectomy in a family with Hereditary Diffuse Gastric Cancer secondary to a CDH1 mutation: A case series.
- Comparative study of endoscopic surveillance in Hereditary Diffuse Gastric Cancer according to CDH1 mutation status.
- Phase II randomized trial of Bethesda Protocol compared to Cambridge Method for detection of early stage gastric cancer in CDH1 mutation carriers.
- Cdh1 and Pik3ca mutations cooperate to induce immune-related invasive lobular carcinoma of the breast.
- ClinVar CDH1 variant entry.
- Germline CDH1 variants and lifetime cancer risk.
- Reproductive decision-making and pregnancy in germline CDH1 variant carriers.
- Adherens junction proteins on the move—From the membrane to the nucleus in intestinal diseases.
- E-Cadherin-deficient epithelial cells are sensitive to HDAC inhibitors.
- Molecular mechanism for strengthening E-cadherin adhesion using a monoclonal antibody. [Monoclonal antibody]
- Identification and optimization of small molecules that restore E-cadherin expression and reduce invasion in colorectal carcinoma cells. [Small molecule drugs]
- Rescue of wild-type E-cadherin expression from nonsense-mutated cancer cells by a suppressor-tRNA.
- Epigenetic activation of E-cadherin is a candidate therapeutic target in human hepatocellular carcinoma.
- Restoration of E-cadherin expression in pancreatic ductal adenocarcinoma treated with microRNA-101.
- Neural crest E-cadherin loss drives cleft lip/palate by epigenetic modulation via pro-inflammatory gene–environment interaction.
- CRISPR/Cas9-mediated activation of CDH1 suppresses metastasis of breast cancer in rats. [CRISPR/Cas9]
- Enhancement of E-cadherin expression and processing and driving of cancer cell metastasis by ARID1A deficiency.
- Curcumin inhibits the proliferation, migration and invasion of gastric cancer cells via the Wnt3a/β-catenin/EMT signaling pathway. [Article in Chinese]
- Geldanamycin abrogates ErbB2 association with proteasome-resistant β-catenin in melanoma cells, increases β-catenin–E-cadherin association, and decreases β-catenin–sensitive transcription.
Join Our Mission
We are working toward a proof of concept for pathogenic CDH1 variants, for targeted, safe gene therapy. If you want to join our mission, we would be glad to hear from you.
