New biomarkers for bowel cancer treatment
One of Europe’s largest collaborative academic-industry research projects, designed to develop and assess novel approaches for identification of new markers for colon cancer, has been conducted by public-private consortium OncoTrack.
Scientists from the OncoTrack Consortium, the Max Planck Institute for Molecular Genetics in Berlin and the company Alacris Theranostics, analysed tumour samples from patients with colon cancer in a preclinical study. The scientists looked for biomarkers, which are molecules that are typical of the different tumour sub-groups and provide valuable information for diagnosis and potential treatment.
The researchers discovered molecules that can predict the effectiveness of two drugs commonly used to treat the disease: Cetuximab, which inhibits the receptor for the epidermal growth factor (EGFR), and the chemotherapy drug 5FU.
The consortium team identified two such biomarkers, which predict whether either the EGFR inhibitors Cetuximab or the chemotherapy 5FU could trigger a successful response in colorectal cancer. Bodo Lange, CEO at Alacris Theranostics said: “The study has revealed a number of exciting findings that have the potential to guide treatment decisions. The extensive molecular and drug sensitivity datasets generated within this study are a highly valuable resource. Our findings provide major new insights into the molecular landscape of colorectal cancer, including the identification of novel alterations, which can be further exploited for advancing understanding of this lethal tumour type and for personalising therapies.”
Bowel cancer is the third most common form of cancer in the world. Colorectal carcinomas currently account for 95% of cases, highlighting the need for better treatment options. Colorectal carcinomas at an advanced stage are one of the most common causes of death, as only some patients respond to drug treatment. Experts don’t know why this is, but it is clear that colorectal carcinomas are very heterogeneous group of cancers.
Bodo Lange states that a “better understanding of this molecular heterogeneity and its impact on drug response is required.”
To be able to predict a tumour’s response to certain drugs more accurately, scientists require detailed information about the molecular profiles of the patients and their tumours.
Scientists at the Charité University Hospital in Berlin and University Hospital Graz found that they were able to better understand the relationships between the molecular pattern of tumours and the response of the tumour to drugs. The scientists collected tumour samples from over 100 colorectal cancer patients at different stages of the disease for their study. These tumours were then grown in tissue culture systems, as well as in special mouse strains, and subsequently treated with a range of medicaments.
The scientists identified the genetic composition of the tumours and analysed their so-called transcriptome, namely the set of all RNA molecules synthesised in a given tissue. Based on this analysis, they were able to produce a definite molecular fingerprint for all of the tumours. The scientists from the Max Planck Institute for Molecular Genetics and colleagues at EPO, Berlin, and Eli Lilly, Madrid, then tested how the tumours responded to different drugs and in this way correlated the tumour fingerprints with their response to the different clinical compounds.
If a group of tumours could be successfully treated using a drug, the scientists looked for typical biomarkers for this tumour type. Up to now, doctors have decided for and against the use of a drug directed against the EGF receptor mainly based on gene mutations. However, the mutation status alone is not specific enough. The knowledge of additional biomarkers could help to improve the individual treatment of cancers.
