Mono- and polyclonal metastases
The main cause of incurable cancer has been discovered
Scientists at Stanford University in the USA have uncovered the mechanism that makes cancer incurable. Metastases, which are the main cause of death in 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 was published in the journal Nature Genetics (Hu et al., Multi-cancer analysis of clonality and the timing of systemic spread in paired primary tumors and metastases).
The researchers determined the nucleotide sequence of the entire coding part of the genome (exome) 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 the treatment contributed to the appearance of mutations and the evolution of cancer cells.
Metastases appear both from one mutated cell or clone (this process is called monoclonal seeding) in the primary tumor, and simultaneously from different clones (polyclonal seeding). It was shown that polyclonal metastases usually developed in the lymph nodes in patients who did not undergo therapy, and less often in tissues distant from the main focus in treated patients. In general, scientists have found that metastases are formed by cancer cells with a small number of mutations unique to secondary foci. This means that metastasis occurred early enough, and the secondary foci are genetically very similar to the primary tumor.
A different picture occurs when late sowing usually involves clones formed when a large variety of mutations are already present in the primary tumor. Then the secondary foci, whose occurrence can be provoked by therapy, are very different from the main neoplasm. As a rule, they consist of drug-resistant cells.
The researchers compared the number of mutations unique to metastases with the number of mutations unique to the primary tumor, and found that the seeding occurred about 2-4 years before the cancer was detected. The earliest metastasis began 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.
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