Experimental drug can reverse immunotherapy resistance

Experimental drug can reverse immunotherapy resistance

Research from the UK’s Institute of Cancer Research and the Royal Marsden has shown that a new drug, guadecitabine, has the potential to overcome resistance to immunotherapy drug Pembrolizumab in cancers like NSCLC, breast cancer and prostate cancer.

Pembrolizumab is a PD-1 immunotherapy drug which aims to unblock your immune system T-cells making them more available to attack the cancer. To date it has been successful in treating cancers such as melanoma and Non-Small Cell Lung Cancer (NSCLC). 

However, some cancers do develop resistance to Pembrolizumab and the cancer starts to progress again.This is thought to occur as the cancer re-methylates, making it stronger. 

The experimental drug, guadecitabine, is a hypomethylating agent and reduces such methylation.

The study involved just 34 patients, 30 of whom also had their cancer analysed for activity and growth. Patients with breast, prostate and lung cancer were included. 18 of the patients had previously had the immunotherapy, and almost half of those had seen cancer progress during treatment.

Overall, 12 of the cancer patients enrolled in the trial had their disease kept in check for 24-weeks or more after receiving the double drug combination - pembrolizumab once per three weeks with guadecitabine for four consecutive days. Those patients’ blood showed the immune system was being activated within the tumours. Of the 12 people who had NSCLC, 10 had had pembrolizumab previous, and 5 had restimulation of immune activity with the combination.

This was the Phase I of the study. 

The side effects reported included neutropenia (58.8%), fatigue (17.6%), febrile neutropenia (11.8%) and nausea (11.8%).

Chris Woollams, former Oxford University Biochemist and a Founder of CANCERactive said, “We think PD-1 drugs like Pembrolizumab and Nivolumab are great drugs, but people are prepared poorly for their introduction in their Treatment programme. Maybe we also have more success with them because we use natural compounds like turmeric simultaneously - there is research (2) showing it is a natural demethylating agent, for example, with breast cancer - and we always rebuild the microbiome first and change patients’ diet, which will also restrict methylation. But it is great to hear from the experts why they think PD-1s stop working too, and to hear that they may have their own solution.”

Go to: How to make your immunotherapy drugs work properly




  1. Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumours - BMJ; Journal for immunotherapy of cancer, Vol 10, Issue 6; Dionysis Papadatos-Pastos et al;

  2. Curcumin from Turmeric Rhizome: A Potential Modulator of DNA Methylation Machinery in Breast Cancer Inhibition; Krystyna Fabianowska-Majewska et al; Nutrients, 2021 Jan 23;13(2):332.


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2022 Research
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