Scientists at Stanford University in the United States have discovered a mechanism that makes cancer incurable. Metastases, the leading cause of death for patients with tumors, may appear several years before the patient is diagnosed. At the same time, drugs trigger natural selection among metastatic cells, making them resistant to therapy. An article with the results of scientific work is published in the journal Nature Genetics.
The researchers determined the nucleotide sequence of the entire coding part of the genome (exoma) in 457 samples of primary tumors and metastases taken from 136 patients with breast cancer, colorectal cancer and lung cancer. At the same time, 100 metastases were exposed to drugs, and 99 remained intact. It turned out that treatment contributed to the emergence of mutations and the evolution of cancer cells.
Metastases appear both from one mutated cell or clone (such a process is called monoclonal culture) in the primary tumor, and simultaneously from different clones (polyclonal culture). It was shown that polyclonal metastases usually developed in the lymph nodes in patients who did not receive therapy, and less often in tissues distant from the main focus in treated patients. In general, scientists found that metastases are formed by cancer cells with a small number of mutations unique to secondary foci. This means that metastasis occurred quite early, and secondary foci are genetically very similar to the primary tumor.
A different picture arises when clones are usually involved in late seeding, formed when a wide variety of mutations are already present in the primary tumor. Then the secondary foci, whose occurrence may provoke therapy, are very different from the main neoplasm. They are usually composed of drug resistant cells.
Researchers compared the number of mutations unique to metastases with the number of mutations unique to the primary tumor, and found that seeding occurred approximately 2-4 years before cancer was detected. The earliest metastasis started in colorectal cancer and lung cancer. Secondary foci are initially weakened, but due to drug treatment, mutations occur that make them more aggressive and resistant to therapy.