A group of researchers from the Stanford University School of Medicine (USA) has shown in a study with 3,000 patients that up to 80 percent of metastatic colorectal cancers spread before their diagnosis.
Colorectal tumor is the second cause of death from cancer in men and women in the United States. In these cases, the metastasis mainly affects the liver and rarely reaches the brain. The genomic changes that cause this cancer are called 'driver mutations'. In this sense, Christina Curtis, professor of medicine and genetics at Stanford and author of the study, has tried to reconstruct the process of metastasis in different patients by analyzing the tumor genome data, with the objective of identifying the drivers .
For the development of this study, published in 'Nature Genetics', researchers have compared genetic mutations in primary tumors of 23 participants with the patterns of their liver or brain metastases to look for similarities or differences between primary and metastatic cancers obtained in the same person.
Then these data have been used to create an evolutionary cancer pattern for each patient. Thus, they have been able to observe that in 17 of 21 patients the metastatic tumors have been initiated by a cell, or a small group of similar cells, that has separated from the primary tumor at the beginning of its development.
"The cells that formed the metastasis were more closely related to the ancestors of the primary tumor than their current relatives," said Curtis, who added that metastasis shared most of the first drivers present in the scheme, presenting few additions. which suggests that "these cancers have acquired a very early metastatic competence during their growth".
Mutations of the PTPRT gene
To further determine when metastasis has occurred, the team has developed a computer program and a statistical method to measure the metastatic propagation time in relation to the size of the primary tumor in an individual patient. In this way, they have been able to observe a similar pattern in most of the cases evaluated. Thus, they applied these theories to 938 people with metastases and 1,813 with non-metastatic cancer.
In this regard, the expert highlighted that mutations of the PTPRT gene were found in most cases with metastatic cancer. Previous studies have shown that the loss of function of this gene increases the activity of the STAT3 protein, which improves cell survival. Thus, researchers have speculated that the inhibition of STAT3 can frustrate tumor growth and metastasis.
"These data indicate that metastasis can occur early in human colorectal cancer and underscores the need for early diagnosis of aggressive diseases. The new biomarkers based on specific combinations of alterations could allow the identification of lethal colorectal tumors at an early stage so that they can be intercepted and adequately treated, "he concluded.