skip to primary navigationskip to content

In quest of new genomic biomarkers for the clinic in Esophageal Cancer

last modified Feb 08, 2019 03:59 PM

Only around 12% of patients survive oesophageal cancer for 10 years or more. This is partly due to late diagnosis, as symptoms often do not present until the cancer is advanced, and partly due to limited treatment options. Oesophageal Adenocarcinoma (EAC) is the main subtype of oesophageal cancer in the UK and is on the rise in western countries – mainly because of lifestyle factors.


A recent study by Frankell et al. from the Fitzgerald group, published this month in Nature Genetics, scans 551 Oesophageal Adenocarcinoma (EAC) samples alongside matched RNA sequencing data from 116 samples of this cohort to provides an exhaustive catalogue of mutations and copy number alterations that are selected for in EAC and could have clinically relevant impact on the prognosis of the disease.

Importantly the study reveals driver mutations for EAC in 99% of patients and that more than half of the mutations (mainly related to Receptor Tyrosine kinases and or Cell Cycle proteins) could be targeted by drugs currently in trials for other cancer types, such as the CDK4/6 inhibitors already approved for breast cancer. This research, could help stratify oesophageal cancer patients to give them more personalised therapies. This in turn could provide options not currently available to patients beyond standard chemotherapy, radiotherapy or surgery. This also means phase II/III clinical trials to treat oesophageal cancer could be feasible in one to two years.

Interestingly, women were found to have more KRAS mutations than men. These mutations are often seen in other cancer types, but are rarely found in oesophageal cancer. This could indicate a different sub-type of the disease in women and suggest they might have a different prognosis or need alternative treatment.


Biological pathways dysregulated by driver-gene mutation and/or CNVs in 551 cases


The study entitled The landscape of selection in 551 esophageal adenocarcinomas defines genomic biomarkers for the clinic by Alex Frankell et al. has been published in Nature Genetics  on 04 February, 2019.