Colorectal cancer (CRC) is one of the most common types of cancer, affecting more than 1 million people globally every year. Although inherited genetic disorders such as the Lynch or the Gardner Syndromes and the familial adenomatous polyposis (FAP) are strongly associated with the development of CRC, they only occur in a small fraction of the population. On the other hand global aging and an unbalanced diet seem to have become prominent risk factors. In light of the aftermaths of the World Health Organization's (WHO) report on the association between red or processed meat consumption and the risk of developing CRC, a better understanding of the best approach to treatment is urgently needed.
Given the statistics around CRC and in view of the large number of people who consume processed meat, it is perhaps not surprising that the report from the WHO’s International Agency for Research on Cancer (IARC) classifying processed meat as carcinogenic to humans caused quiet a stir.
The link between a high consumption of red meat and the risk of developing cancer is not recent news. Already in 2011 the UK's Department of Health asked to an independent scientific advisory committee on nutrition (SACN) to issue a report on this matter. SACN expert found the association to be so strong that they recommended individuals who eats at least 90g of red meat per day to cut down to 70g daily to lower their risk.
Recently the IARC experts took a rigorous scientific approach by reviewing more than 800 studies investigating the associations of several types of cancer with the consumption of red or processed meat. By doing so they concluded that the consumption of red meat is “probably carcinogenic to humans”; however they found “sufficient evidence that the consumption of processed meat causes colorectal cancer”, and they gave processed meat a similar ranking as smoke, alcohol and asbestos.
However alarming these data may sound, experts warned that red meat has nutritional values too and prompted governments and international regulatory agencies to conduct risk assessments, in order to balance the risks and benefits of eating red and processed meat and to provide the best possible dietary recommendations.
From Bettering our Diet to Improving Current Treatment
Although it is important that a global effort is made to try and reduce CRC risk factors to prevent the disease from developing, it is as vital to ensure that patients currently been diagnosed or undergoing treatment receive the most appropriate therapy.
About 50% of CRC cases present with metastatic disease (mCRC), which is generally associated with poor prognosis.
mCRC treatment entails the use of radiotherapy, chemotherapy or targeted agents, depending on the stage of the disease. Patients that display aberrant epidermal growth factor receptor (EGFR) activation and are negative for KRAS mutation could benefit from antibodies therapy, (cetuximab or panitumumab) targeting EGFR. However it is unclear why some of the patients fitting these criteria still do not respond to treatment. It is therefore essential to identify additional biomarkers of response that can be successfully used in the clinic to stratify the patient population.
At Crown Bioscience we set to address this issue by analysing the response to treatment on a large cohort of CRC patient-derived xenograft (PDX) models that have been used as patient avatars in mouse clinical trials (MCT or HuTrial™). Our MCT enrolled 27 EGFR expressing PDX and was designed to experimentally test the roles of KRAS mutations, along with the activating mutations of other oncogenes in responses to cetuximab. Our data suggest that the presence of a wild type form of KRAS is not sufficient to predict response to cetuximab. However we could identify a small number of well-known oncogenic mutations with a better predictive power than KRAS that could possibly be used in the clinic as biomarkers of response.
To talk to us about how we can help positioning your drug or for more information on our CRC PDX models please email us at busdev@crownbio.com
DISCLOSURE STATEMENT
Crown Bioscience provides preclinical models and services for translational oncology and is not qualified to provide medical advice. For more information on clinical trials recruitment and current treatment options please refer to your doctor or visit the National Cancer Institute (NIH) and the National Health Service (NHS) websites.
