Metastases metastases strife | Science and life

We are accustomed to the fact that the various properties of malignant cells are explained by their various mutations. Once we wrote that, for example, in a three-centimeter liver tumor there can be almost a hundred thousand different defects in DNA. These defects are distributed differently in cells, but one way or another, among them there may well be those that, due to mutations, are resistant to one type of therapy, and those that are resistant to another type of therapy, and those that tend to come off. away from the tumor and go on a metastatic journey. Actually, when a tumor begins to be treated, it deliberately begins to repair its DNA worse – in this way, cancer cells will quickly receive many new mutations, among which, of course, there will be many harmful ones, but there will also be useful ones that help survive therapy.

At the same time, from time to time we see reports that tumors exhibit their malignant properties without additional mutations. That is, there are some initial cancerous mutations in malignant cells, but they sometimes resist drugs without new changes in DNA. And even for metastases, it is not so much new mutations that are needed, but a weakening of the immune defense, otherwise cancer cells already have everything for settling to new places. But here, as the staff found out Hartwig Medical Foundation and Utrecht University, it all depends on the specific tumor. In two articles in Nature and Nature Genetics researchers published results comparing primary tumors and those that grew from metastases; samples taken from more than 7,000 people were classified as seventy-one types of cancer.

In fact, this is one of the works on the molecular taxonomy of mutations, of which quite a lot has appeared recently. Comparison of mutations in primary and metastatic tumors has been done before. However, the search for mutations, the search for similarities and differences between primary and metastatic tumors have so far been done by methods that differed somewhat from each other, from the isolation of tumor cells to algorithms that compare read DNA sequences. Researchers who used different methods had their reasons for doing this, but in such cases there is always a chance that what was able to be seen by one method, another method will miss, and vice versa. Therefore, the value of the new results is that a huge mass of tumors were processed with the same analytical tools. And now many previous conclusions have received one more, more reliable confirmation.

We named one of the main results: when a tumor metastasizes, it does not have to have any new mutations, it all depends on what kind of tumor we are talking about. For example, in the case of pancreatic cancer, the mutational differences between the primary tumor and the secondary (that is, formed as a result of metastasis) are practically negligible. But secondary tumors that come from prostate cancer, or thyroid cancer, or some forms of breast cancer, are quite noticeably different in a genetic sense from the primary tumor. At the same time, it cannot be said that metastases acquire certain genetic features that do not exist in primary tumors. We are talking about the fact that in the genetic portrait of a secondary tumor, certain features that were shaded in the primary one stand out more strongly (if they stand out). And, of course, there are many genetic traces left in metastatic tumors that indicate a struggle with drugs – after all, metastatic cells usually come from a tumor that has already been treated with something. At the same time, it has now been possible to detect genetic changes that are clearly associated with drug resistance of tumors, but which have not yet come to the attention of researchers.

Another set of results is associated with the escape of cancer cells from the immune system. As you know, the immune system must catch and destroy cancer cells, but they somehow manage to deceive it. Due to the fact that cancer cells become invisible to the immune system, immunotherapy methods do not work effectively. And here, too, the genetic characteristics of malignant cells come into play.

With some types of cancer, it is rare in which patients it is possible to find pronounced anti-immune features in malignant cells. And with some, the opposite is true: for example, with cervical cancer, such features are found in half of the patients. If we talk about primary tumors and metastases, then there are almost no differences between them in the ability to avoid the attention of the immune system.

If the primary tumor was well hidden from the immune system, then its metastases will also be well hidden, and if it was poorly hidden, then the metastases will also have to experience frequent immune attacks. At the same time, the ability to hide from immunity is proportional to the overall mutability of the tumor: if there are a lot of mutations in it at all, then with a high probability it will be absolutely invisible to the immune system. If there are few mutations in the tumor as a whole, then the immune system will notice tumor cells quite often (although the fact that the tumor did appear suggests that it has some kind of anti-immune tricks).

All this once again indicates a wide variety of tumors and the need for a thorough molecular genetic analysis in each individual case. Fortunately, DNA analysis is becoming cheaper year by year, and, probably, in the near future, individual treatment regimens will be drawn up for each cancer patient, based on the genetic portrait of his tumor, whether primary or secondary.