Madrid
Updated:05/30/2022 13:59h
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The main treatment for colon and rectal cancer, chemotherapy, does not work in all patients. In an important group, 30%, resistance is generated and the tumors cause metastases. They are patients with a poor prognosis.
Now, a team of researchers led by the Hospital del Mar Medical Research Institute has discovered what causes this chain of events. In this way, they have been able to determine a set of poor prognosis markers and a potential therapeutic target for these patients. The work is published in the journal Nature Communications.
In some cases and for various reasons, the chemotherapy treatmentit is not enough to eliminate all the cells of the tumor and a part of them survives, passing to an embryonic state.
From here, the tumor can reappear with more force, being able to resist treatment and metastasize.
Researchers have reproduced this process in organoides created from patient cells and have been able to verify that a set of genes are expressed in cells that are in this embryonic state, specifically, a group of eight genes, which are characteristic of these tumor cells and make them more aggressive .
Given this, Laura Solé and the Theresa Wolf, main authors of the work and researchers at IMIM-Hospital del Mar and CIBER Cancer (CIBERONC), state that “this embryonic signature can serve as a tool to predict the prognosis of patients and to be able to consider specific treatments for them”. The results were validated in in vivo tests with human tumors implanted in mice.
Possible therapeutic target
The researchers consider that knowing the factors involved in the process of embryonic conversion of tumors will allow establishing the risk of relapse in patients with colon and rectal cancer. “We have seen that cells that are not killed by chemotherapy make this embryonic conversion and we believe that this is also what happens in a proportion of tumors even before treatment in patients, cells that chemotherapy does not kill, develop this phenotype. embryonic”, explains Lluís Espinosa, main author of the study, coordinator of the Molecular Mechanisms of Cancer Research Group and of the Stem Cells of the IMIM-Hospital del Mar and researcher of the CIBERONC.
Now, work is being done to take advantage of this discovery not only in the prognosis of patients, but also to be able to determine new treatments and personalize the approach for this type of higher-risk patients. Identifying the specific regulator of the embryonic conversion of these cells will make it easier to apply a new way of treating these cases, combining chemotherapy and specific inhibitors of the genes involved. At this time, there are already some drugs that can act on tumors with embryonic characteristics.
In fact, the intention of the authors of the work is to develop a kit which, from patient samples, makes it easier to determine if these genes are present. As he points out Espinosa“once the factor that causes conversion in these patients has been identified, this signature could be detected to determine who are candidates to receive a specific treatment directed at these genes.”
In this sense, Marta Guix, also a signatory to the work and an assistant doctor at the Hospital del Mar Medical Oncology Service, considers that “when you treat patients with colon and rectal cancer, one of the first lessons you learn is that each case is different, not only because each person is unique, but because the tumors they suffer from also have very heterogeneous behaviors. Research work like this allows us to understand why there are so many differences and what may be the best way to treat each case. There is still a lot to do, but without a doubt an exciting path opens up for us».
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