Work from the Rosenfeld and Brenton labs has spun out into a clinical cancer genomics company, Inivata, that is transforming the lives of cancer patients and their families through the power of liquid biopsy.

 

The ability to track how tumours evolve in real-time and develop drug resistance is an important step in identifying new, effective treatments for cancer. Cambridge scientists created a new way of looking at tumour evolution by monitoring changes in DNA found in patients’ blood. This research led to a spinout from CRUK and the University of Cambridge, Inivata Ltd., a clinical cancer genomics company harnessing the potential of circulating tumour DNA analysis. Liquid biopsies offer a non-invasive picture of tumour heterogeneity and crucially are available when a tissue biopsy is limited or unobtainable, resulting in improved access to genomic testing and targeted treatment for oncologists and their patients.

Cancers acquire resistance to systemic treatment because of clonal evolution and selection. Repeat biopsies to study genomic evolution, as a result of therapy, are difficult, invasive and may be confounded by intra-tumour heterogeneity. Recent studies have shown that characterisation of genomic alterations in solid cancers can be complemented by sequencing of circulating tumour DNA (ctDNA) released from cancer cells into plasma, representing a non-invasive liquid biopsy.

The origin of circulating biomarkers for gliomas. 

The underpinning research, co-directed by Dr James Brenton, Professor Carlos Caldas, and Dr Nitzan Rosenfeld from the University’s Cancer Research UK Cambridge Institute, followed patients with advanced breast, ovarian and lung cancers and took blood samples, across years of treatment. In one study, they focused analysis on samples that contained relatively high concentrations of ctDNA. By looking for changes in the ctDNA before and after each course of treatment, they were able to identify changes in the tumour’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. In another study, Tim Forshew and Davina Gale at the Rosenfeld lab developed sensitive methods for targeted sequencing that can identify genomic alterations in cancer when their levels are low and hard to detect.

“Importantly, this advance means that we are able to screen multiple 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, and is an enabling tool for genomic medicine for cancer.”– Dr James Brenton.

In 2014, these liquid biopsy methods led to the spin out company Inivata, co-founded by Rosenfeld, Brenton, Forshew and Gale. Inivata raised £4M of initial venture capital investment, and a further £31.5M in 2016. By 2018 Inivata had made large improvements to the method and in parallel to generating data for research, was generating molecular pathology data from patient plasma samples through a validated assay that was approved for clinical use through a CLIA-certified lab in the US. Inivata’s platform brought together Next-Generation Sequencing (NGS) technology with proprietary algorithms and databases. Using its best-in-class liquid biopsy platform called InVision®, they can detect and characterise ctDNA via a simple non-invasive blood test, enabling healthcare professionals to continuously monitor and adapt their patient’s treatment, personalising cancer care.

References:

Murtaza M., et al. Nature. 2013 2; 497(7447):108-12.

Forshew T., et al. Science Translational Medicine, 2012 May 30; 4(136):136ra68.

Wan J. C. M., et al. Nature Reviews Cancer, April 2017; 17(4):223–238.

Davina Gale et al Plos One 2018


This work was supported by Cancer Research UK, the University of Cambridge, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Hutchison Whampoa Limited. Inivata’s work is supported by investment by -IP Group, Cambridge Innovation Capital, Johnson & Johnson Innovation and Woodford Patient Capital Trust.