By tracking changes in patients’ blood, Cambridge scientists have created a new way of looking at how tumors evolve in real-time and develop drug resistance. The research was published in Nature.
Scientists at the Cancer Research UK Cambridge Institute at the University of Cambridge used traces of tumor DNA, known as circulating tumor DNA (ctDNA), found in cancer patients’ blood to follow the progress of the disease as it changed over time and developed resistance to chemotherapy treatments.
For the study, which was co-directed by Dr. James Brenton, Professor Carlos Caldas and Dr. Nitzan Rosenfeld, from the University's Cancer Research UK Cambridge Institute, they followed six patients with advanced breast, ovarian and lung cancers and took blood samples, over one to two years. They then focused analysis on those samples that contained relatively higher concentrations of tumor ctDNA.
By looking for changes in the tumor ctDNA before and after each course of treatment, they were able to identify changes in the tumor’s DNA that were likely linked to drug resistance following each treatment session.
Using this new method, they were able to identify several changes linked to drug-resistance in response to chemotherapy drugs such as paclitaxel (taxol) which is used to treat ovarian, breast and lung cancers, tamoxifen which is used to treat oestrogen-positive breast cancers and transtuzumab (Herceptin) which is used to treat HER2 positive breast cancers.
The researchers hope this new approach could facilitate research on how cancer tumors develop resistance to some of our most effective chemotherapy drugs as well as providing an alternative to current methods of collecting tumor DNA– by taking a sample direct from the tumor– a much more difficult and invasive procedure.
“Tumors are constantly changing and evolving which helps them develop a resistance to many of the drugs we currently give patients to treat their disease. We’ve shown that a very simple blood test can be used to collect enough tumor DNA to suggest to us what parts of the cancer’s genetic code is changing and creating tumor resistance to chemotherapy or biologically-targeted therapies," Rosenfeld says. “We hope that our discoveries can pave the way to helping us understand how cancers develop drug resistance as well as identifying new potential targets for future cancer drugs.”
Brenton adds: "Importantly, this advance means that we will be able to screen a much larger number of genes in the blood to test if specific genetic changes in the cancer explain resistance to treatment. The low cost and high acceptability of a blood sample means that this can be done across hundreds or thousands of patients. This is vital to discover reliable clinical biomarkers."
"The tracking of different cancer clones in real time using a liquid biopsy will have enormous value to identify drug resistance in the clinic and adjust therapy accordingly," says Caldas says.
The Cancer Research UK Cambridge Institute is a major research centre which aims to take the scientific strengths of Cambridge to practical application for the benefit of cancer patients. The Institute is a unique partnership between the University of Cambridge and Cancer Research UK. It is housed in the Li Ka Shing Centre, a state-of-the-art research facility located on the Cambridge Biomedical Campus which was generously funded by Hutchison Whampoa Ltd, Cambridge University, Cancer Research UK, The Atlantic Philanthropies and a range of other donors. For more information visit www.cruk.cam.ac.uk.
Source: University of Cambridge