One out of every four people with bowel cancer is resistant to treatment with conventional chemotherapy. For these people, new weapons in the therapeutic arsenal to fight the disease and eradicate it from the body are essential. Researchers of the IMIM research group on Molecular Cancer Therapy, led by Joan Albanell and oncologists from Hospital del Mar, have led an international study that has added a new-generation drug that is more powerful and effective in these cases.

Sym004, as the new drug has been called, consists of a mix of monoclonal antibodies that have shown to work when more familiar treatments such as Cetuximab and Panitumumab stop working. The new drug has shown its efficacy in bowel cancer cell lines in animal models and in some human patients, laying the necessary scientific groundwork for starting a clinical trial in oncologic centers of excellence. This trial is in the design phase and will be carried out soon.

 

Sym004, as the new drug has been called, consists of a mix of monoclonal antibodies that have shown to work when more familiar treatments such as Cetuximab and Panitumumab stop working. The new drug has shown its efficacy in bowel cancer cell lines in animal models and in some human patients, laying the necessary scientific groundwork for starting a clinical trial in oncologic centers of excellence.

 

Liquid biopsy and personalized treatment

Just as important as providing the most appropriate treatment is knowing beforehand the probability of each patient being resistant to the treatment, of being one of this 25% of people with a mutation of the oncogene EGFR. This is the line of work that was begun by the research group some years ago when only mutations of the oncogene KRAS were known; it has led to considerable knowledge and expertise regarding mutations of EGFR, which has been found to condition response to treatment. In 2013, with the goal of personalizing treatments and being able to predict who may be resistant, kits for detecting these mutations were patented in collaboration with the biotech company Biocartis. Thanks to this initiative, the detection kits are now available to any center that wishes to use them to apply precision medicine and prevent valuable time being lost through inefficient treatment in people who are expected to have this mutation.

Knowing that the gene will mutate means that the right initial choice can be made by selecting the most appropriate drug. A tailored treatment that also prevents potential side effects of traditional, less accurate, chemotherapy. The detection tests are also very simple, fast and efficient to perform by means of what is known as a liquid biopsy, on ultrasequencing platforms using Beaming technology that analyzes tumor DNA circulating in the blood. They allow for very accurate monitoring of the tumor, like a photograph of the status of the tumor at the molecular level, and can be repeated to determine the mutations have been kept at bay. It may sound complex but it is nothing like a traditional invasive biopsy. For the patient, it involves a simple blood sample and a whole host of advantages.

 

New weapons of mass destruction for bowel cancer

Now, as well as being able to detect patients who may be resistant, with Sym004, we will have a drug that directly overcomes the difficulties involved with previous treatments, as soon as the clinical phase is completed and it reaches hospitals and general patients. Research into new drugs that help to avoid resistance to treatments or mutations in the drug receptors on these genes or other genes that we are not yet aware of continues to be the challenge facing researchers. The search for new treatments that help to overcome the disease in all patients with bowel cancer continues unceasingly. Researchers are already taking part in a new international project to study another option, called MM151, that shares many aspects with Sym004. The goal is to have the option of a targeted treatment and to always have another option when previous treatments fail. The results of these studies are so encouraging that new clinical trials are already being designed in collaboration with the Vall d’Hebron Institute of Oncology (VHIO) and with two Italian centers, and recruitment of the first patients has already begun.

 

 

Reference article

Sanchez-Martín FJ, Bellosillo B, Gelabert M, Dalmases A, Cañadas I, Vidal J, Martinez A, Argiles G, Siravegna G, Arena S, Koefoed K, Visa L, Arpi O, Horak ID, Iglesias M, Stroch C, Kragh M, Rovira A, Albanell J, Tabernero J, Bardelli A, Montagut C. The first-in-class anti-EGFR antibody mixture Sym004 overcomes cetuximab-resistance mediated by EGFR extracellular domain mutations in colorectal càncer. Clin Cancer Res. 2016 Feb 17. pii: clincanres.2400.2015.

http://clincancerres.aacrjournals.org/content/22/13/3260