Method to test efficacy of chemotherapy found by Cambridge researchers

Joanna Taylor 22 December 2016

Researchers at the Cancer Research UK Cambridge Institute, in collaboration with the University and various affiliated research groups, have investigated how mutations in a specific gene can help understand the potential efficacy of chemotherapy to a specific ovarian cancer.

Currently the gold-standard measurement for determining how a patient will react to chemotherapy is measuring their levels of the protein CA-125, a test which can be used to screen for early onset ovarian cancers. This protein is present in the cornea and the female reproductive tract: elevated levels may be an indicator of the progression of ovarian cancer.

This technique has drawbacks, however, because CA-125 levels may be elevated due to other relatively benign diseases as well as the gene being correlated to non-ovarian cancers which limits its specificity.

The team, headed by James Brenton, assessed genetic material from patients with High Grade Serous Ovarian Carcinoma (HGSOC) before and after treatment. HGSOCs are the most common ovarian cancers, and also have the lowest survival rates. The study assessed the quantity of the gene TP53 (which regulates the cell cycle and so is important to supress tumour progression) present in circulating tumour DNA (DNA from tumours that is not bound to cells but flows freely in the patient’s blood, ctDNA).

ctDNA is a useful marker of HGSOC as 99% of patients present a mutation in the TP53 gene. The study found that the fraction of mutated TP53 genes in ctDNA had a correlation to the volume of tumours present in the patients as measured using 3D CT scans, and so tracking allowed the team to understand how the cancer was progressing, which is not possible using the CA-125 method.

After one round of chemotherapy, patients’ ctDNA was measured again and those who showed a decrease in the fraction of mutated TP53 of greater than 60% were found to have their cancers worsen after more than 6 months. Those whose fraction decreased by less than 60% had much quicker progression of their disease.

The results of this study suggest that monitoring ctDNA of women diagnosed with HGSOC might enable easier prognosis and be an indicator of how well chemotherapy will work. The study was limited however, as it used data from patients with various treatment methods and some of the cancers were relapses.

A more homogenous group of patients and treatment methods will be needed to give greater insight into the potential utility of monitoring ctDNA.