Researchers find a 'less is more' approach to drug dosage could help tackle hard-to-treat cancers

As aggressive cancers like pancreatic cancer and glioblastoma grow they develop a chaotic system of blood vessels around tumours, forming an impenetrable jungle that makes it difficult for treatments to reach the cancer cells. Overcoming this is a key step in creating cures that work for more patients. Thanks to our Curestarters, researchers in Australia have recently made the surprising discovery that lowering the dose of some anti-cancer drugs can tame this jungle, allowing immunotherapy access to tumours so it can fight cancer cells more effectively.

My team and I thank all supporters for their trust in our research. We all share the same goal and strive to develop new treatment options for a better future. Now we can hopefully produce an outcome which lends itself to better, more effective treatments for the very sick and prolonging their lives.

A shot of Ruth Ganss in the lab, holding a pipette and looking straight at the camera
Professor Ruth Ganss University of Western Australia
Our body's immune system has incredible capabilities to fight cancer - harnessing this is what is known as immunotherapy. 

To be effective, the body’s immune cells need to get through the dense blood vessel barrier that surrounds tumours and into cancer cells. One approach to tackling these types of cancers is to use drugs that shut down the blood vessels around the tumour entirely. By restricting the blood flow to a tumour, we can stop it from being able to grow. But stopping the flow of blood to the tumour also stops immune cells from being able to enter. 

An image of an abnormal tumour blood vessel (represented in red) with no substantial activation (represented in yellow)
An image of a tumour blood vessel following low dose treatment with activation (represented in yellow) to enable immune cell access into tumour

That is why Professor Ruth Ganss and her team wanted to explore whether using a very low dose of trametinib, a cancer growth blocker drug, and then immunotherapy could be a more effective treatment than attacking cancer cells with high dose trametinib alone.

They discovered that by reducing the dosage to a hundred times lower than typically used, the drug re-structured the blood vessels around the tumour so they could now let immune cells in.

These images show tumour blood vessels before (first image) and after (second image) treatment. Yellow areas show where immune cells are able to access the tumour. You can see that after treatment, the chaotic structure of the blood vessels has become more organised, and there are a lot of yellow areas where immune cells can now work effectively.

This discovery opens up new possibilities for hard-to-treat cancers like pancreatic cancer and glioblastoma that develop this blood vessel barrier.

Aggressive cancers like these currently have very low survival rates - only 10 in 100 patients with pancreatic cancer will survive 5 years or more after their diagnosis, and only 7 in 100 will for glioblastoma.

But the ability to control blood vessels and allow immunotherapy to work against tumours is a huge stepping stone towards more effective treatments. And as the drugs that Professor Ganss and her team are investigating are already approved, the process of getting this new treatment strategy to patients is streamlined – it could just be a matter of changing the dose.

The team hope clinical trials can start soon to test how this works in patients with glioblastoma, and the doctors they have worked with are very excited by the potential this discovery holds. Currently, patients diagnosed with hard-to-treat cancers face bleak statistics for their survival. If clinical trials go well, this new treatment strategy could offer more options to these patients and prevent many lives from being cut short too soon.

Ruth Ganss Teamshot

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