Normal cells help cancer cells survive during chemotherapy

Sometimes cancer cells can resist chemotherapy from the very beginning: as it turns out, they receive this “gift” from proteins in healthy cells surrounding the tumor.

In modern medicine, cancer is treated by targeting the tumor. A specific mutation is sought in cancer cells, and the drug is aimed at a specific cancer mutant protein. This type of chemotherapy is much better than conventional chemotherapy, which floods the entire body with poison, which affects not only the tumor, but also healthy tissue.

At the same time, the effectiveness of such therapy in laboratory conditions is incomparable with clinical results. Cancer cells in a test tube die together from a drug specially created for them - and in patients, all this has only a partial and (or) temporary effect. For example, this is the case with melanoma: an inhibitor of the RAF protein was created to treat this type of tumor, which has a specific mutation in melanoma cells. In some patients, the response to therapy was more than noticeable, and malignant cells almost completely disappeared, and in other cases, the tumor only retreated slightly, demonstrating amazing resistance. And here it is worth clarifying that this is not an acquired trait: drug resistance that appears in cancer cells after therapy is another, albeit more familiar problem of oncology. In this case, it is as if the cancer cells initially have something that protects them from death as a result of targeted treatment with the drug.

This mystery was solved by two research groups - from Genetech and the Broad Institute (USA). Genetech specialists tested 41 lines of various cancer cells, from breast tumors to lung and skin tumors, for primary drug resistance. In an article published in the journal Nature, they write that the cells resisted the drugs only in the presence of a protein cocktail taken from the tumor stroma - that is, from the normal cells surrounding the tumor and serving as its support.

The second group of scientists grew several types of cancer cells, again adding normal ones to them. The cancer cells grown alone died from the drugs, but if normal cells were added to them, the tumor survived in more than half of the cases. That is, it turns out that the legendary immortality of cancer is at least partly provided by healthy tissues. In an article published in the same journal, researchers from the Broad Institute report that they have managed to identify a protein secreted by normal cells that helps cancer cells survive the “chemical attack.” About 500 secreted proteins were analyzed, and in the end, the “last resort” was HGF, or hepatocyte growth factor. It binds to one of the receptors of cancer cells, as a result of which melanoma cells become resistant to the drug targeting the mutant RAF protein. It was previously established that the hyperactivity of this receptor is related to tumor growth.

These results were confirmed in clinical experiments. In patients with high HGF levels, targeted antitumor therapy did not produce the desired effect, whereas with low HGF levels, the drug caused a sharp reduction in the tumor. That is, for a full-fledged treatment, it is necessary to hit not only the cancer protein itself, which is important for the life of the cancer cell, but also the receptor, with the help of which the cancer cell receives help from healthy ones.

The findings have enormous fundamental and practical significance, but translating them into everyday clinical practice will be very difficult. The HGF help protein may be important only for melanoma, which the researchers worked with. Other cancers may use different proteins, and for each of them, a lot of work is needed to identify these proteins.

In this regard, the question arises: will chemotherapy regain its advantage, since it kills healthy cells along with cancer cells and is thus capable of depriving the tumor of any hope of salvation?

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