Eden Ben, CEO of Amorphical, and Dr Yigal Blum, CTO of Amorphical, argue that targeting the hostile tumour microenvironment is the key to effectively treating this aggressive cancer. 

For years, the conversation around pancreatic cancer has focused on the tumour itself, the “broken” cells that won’t stop growing. In 2026, our toolbox for attacking those cells continues to grow. We’re using AI to help detect lesions earlier than ever and CRISPR “genetic scissors” to target the specific mutations driving the disease. However, the fact remains that for stage IV patients, the one-year survival rate is 25% and the five-year survival rate remains remarkably low at around 3% (1). 

We believe the missing link in treating late-stage patients may lie in targeting the hostile tumour microenvironment in tandem with conventional symptom management. By the time pancreatic tumours are discovered, they have typically built a protective ‘fortress’ of dense, scar-like tissue and a highly acidic microenvironment. This acidic shield acts like a chemical barrier, impairing the best treatments – from standard chemo to the latest gene therapies – before they fully penetrate cancer cells, while also suppressing the immune system’s ability to recognise and combat malignant cells. 

For decades, the strategy has been to simply use aggressive drugs and treatments to manage the symptoms of the disease, but that hasn’t significantly changed the outcome. To move the needle of survival rates, we need to stop just fighting the symptoms and start addressing the physiological problem.  

A growing body of research focuses on how to neutralise this environmental acidity, which aims to alleviate the conditions that prevent the immune system from effectively combatting tumour cells. 

How tumour acidity protects cancer

Malignant tumours create an acidic environment through a well-recognised mechanism, known as the Warburg Effect (2). This means cancer cells metabolise sugar for energy in a way that produces high amounts of lactate in parallel with the release of the acidic hydrogen ions. These ions are pumped out of the cancer cells and into the surrounding space, causing a local acidic environment, defined as acidosis. 

This acidity is not a mere side effect, it is a tactical defense that helps cancer cells survive in three ways: 

1. Immune Silencing: It “blinds” T-cells and natural killer cells, preventing the body’s natural defenses from recognising or attacking the tumour.
2. Tissue Invasion: It activates specific enzymes that break down healthy tissue, paving the way for the cancer to spread to other organs.
3. Treatment Neutralisation: It creates a pH barrier that can physically degrade or neutralise chemotherapy drugs like FOLFIRINOX before they can ever work.

Nano-amorphous minerals: A bio-inspired solution

A potential solution to this problem was discovered from an unlikely source: the blue crayfish, a crustacean that rapidly regenerates its shell after moulting. It does this by producing a unique form of mineral called nano-amorphous calcium carbonate (ACC). Unlike crystalline calcium carbonate found in chalk, marble, and dietary supplements, ACC lacks a crystalline structure, making it more soluble and more readily absorbed by the body. 

Through nanotechnology, this molecule has been synthetically reproduced and stabilised so it can be studied as an investigational compound. Due to its unique structure, ACC has a high surface area and a natural attraction to acidic areas. When ACC reaches an acidic tumour environment, it dissolves, releasing carbonate that subsequently converts into bicarbonate ions. These ions act as a buffer that raises the pH level and normalises the organ acidity (3).

Biological effects of normalising pH

When the acidotic environment of a tumour is reduced, several biological changes occur. Early research suggests that restoring the normal pH can shift cancer cells back toward a more normal metabolism (4). This may also reactivate the immune system so it can recognise and attack the tumour. 

It represents a non-cytotoxic strategy, which means it is not designed to directly kill the cells. Rather, the approach aims to dismantle the immune-protective environment the tumour creates for itself, potentially allowing the patient’s immune system and standard medical treatments to function more effectively.

Clinical observations and current research

We are currently investigating how alkaline nano-amorphous compounds work when given alongside standard chemotherapy treatments like FOLFIRINOX through compassionate use channels. While individual cases do not provide scientific proof of efficacy, we have seen encouraging improvements in patients suffering from advanced pancreatic cancer. 

For example, in a clinical case report on file (5), a 73-year-old female with stage IV pancreatic ductal adenocarcinoma (PDAC), with malignant invasion of the stomach and major blood vessels, began treatment with FOLFIRINOX in combination with nano-amorphous minerals. Over the following 16 months, PET CT imaging demonstrated a partial regression of the primary pancreatic lesion and the complete elimination of a secondary rectal lesion. Additionally, the patient reported significant improvements in well-being, as well as weight gain. She has been able to return to her normal daily activities while continuing maintenance therapy alongside nano-amorphous minerals support. 

In a separate unpublished case (6), a 60-year-old female suffering from jaundice, weight loss, and abdominal pain, was diagnosed with stage IV pancreatic head adenocarcinoma, confirmed by imaging and a biopsy. After undergoing a Whipple procedure and portal vein resection, she began adjuvant chemotherapy treatment, in combination with nano-amorphous substances. Seven months after her diagnosis, she completed the adjuvant therapy and reported feeling well with no pain. A surveillance PET-CT scan revealed no evidence of recurrent disease with no pathological findings, suggesting a state of remission and improved quality of life. 

These preliminary clinical observations are consistent with preclinical and mechanistic evidence demonstrating the buffering-based anti-cancer activity of the nano-amorphous minerals, as previously reported in preclinical experimental models (3). Consequently, a formal Phase II clinical trial is currently underway (7). This trial will provide more evidence and data about the efficacy of this therapeutic approach in a larger group of patients.

Modulating the microenvironment to reach the tumour

The future of treating solid tumours such as pancreatic cancer may depend on the ability to modulate the tumour’s acidic microenvironment, which is a primary driver for resistance or failure of standard care therapeutics. Alkaline nano-amorphous minerals are being developed as a precision solution to address this physiological barrier through controlled release and targeted buffering of the tumour environment. 

By utilising the unique solubility and bioavailability of this active compound, we are investigating the targeted buffer delivery directly to the malignant site. It is intended to fundamentally shift the chemical environment of the tumour rather than just manage the symptoms. While still at an early clinical stage, pH modulation of damaged microenvironments with the developed nano-amorphous substances may open the door for new combination therapies that were previously inhibited by low pH levels. 

The goal is to move beyond the traditional cytotoxic therapies and evaluate a safe approach as a potential foundational tool in oncology. This approach aims to restore the effectiveness of existing therapies and reactivate anti-tumour immune responses. It presents a shift toward a more effective path to help patients recover from one of the most difficult-to-treat cancers.

References

1. American Cancer Society. Survival Rates for Pancreatic Cancer (Cited December 28, 2025). Available from: https://www.cancer.org/cancer/types/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html 
2. Zhang H, Liu S, et-al. Novel insight into the Warburg effect: Sweet temptation. Critical Reviews in Oncology/Hematology 2025;214:104844.
3. Natan Y, Blum Y, et-al. Amorphous Calcium Carbonate Shows Anti-Cancer Properties That are Attributed to Its Buffering Capacity. MDPI, Cancers 2023;15(15). 
4. Tafech A, Stéphanou A. On the Importance of Acidity in Cancer Cells and Therapy. MDPI, Biology 2024;13(4):225.
5. Case Study Data: Internal clinical records, Amorphical, 2024. (Unpublished).
6. Case Study Data: Internal clinical records, Amorphical, 2024. (Unpublished).
7. PR Newswire. Amorphical Announces Positive Final Long-Term Results from Phase 2 Crohn’s Disease Trial: Results Confirm Efficacy and Show Sustained Clinical Remission (Cited December 28, 2025) Available from: https://www.prnewswire.com/il/news-releases/amorphical-announces-positive-final-long-term-results-from-phase-2-crohns-disease-trial-results-confirm-efficacy-and-show-sustained-clinical-remission-302643241.html 

About the authors

Eden Ben is a biomedical engineer and the CEO of Amorphical, a clinical-stage biotechnology company pioneering nano-amorphous mineral pharmacologic agents. He earned his BSc in medical engineering from Afeka Academic College of Engineering, where he specialised in the mechanics of physiological systems. 

Dr Yigal Blum, PhD, is Chief Technology Officer at Amorphical, where he leads scientific development of the company’s nano-amorphous mineral platform. He brings more than three decades of experience in applied chemistry, materials science, and nanotechnology, including 35 years at SRI International’s Chemical Science and Technology Laboratory. Dr Blum holds a PhD in Organometallic Chemistry from Tel Aviv University. He has published over 70 peer-reviewed articles and holds over 100 patents. 

From DDW Volume 27 – Issue 2, Spring 2026 – Read the digital issue here

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