A new U.S. study found that chemotherapy, while targeting and killing tumor cells, also stimulates surrounding normal cells to release a chemical that stimulates tumor cell growth, ultimately leading to treatment tolerance (treatment recurrence). The researchers hope that their findings will lead to better therapies and buy precious time for patients with advanced cancer. Author Peter S. Nelson, of the Division of Human Biology at the Fred Hutchinson Cancer Research Center in Seattle, and his colleagues published their findings in the Aug. 6 online edition of Nature Medicine. Nelson told the press, “Tumor cells in the human body live in a very complex environment. Both the location of the tumor cells and the cells in their vicinity affect the tumor cells’ response and resistance to treatment. Therefore, chemotherapy is often discarded in the treatment of patients with advanced cancer because the dose of chemotherapy administered to the patient to destroy the tumor is sufficient to kill the patient. In the laboratory, it is possible to “cure” almost any tumor by administering high doses of toxic chemotherapy agents to tumor cells in a petri dish, Nelson said, but this is not possible for patients because high doses of chemotherapy drugs will kill not only tumor cells but normal cells as well. “ The researchers hint that their findings could pave the way for the development of more efficient tumor therapies. Smaller doses of agents are given periodically to well-formed tumors, giving normal cells time to recover in between doses. The downside to this, however, is that it may not kill all the tumor cells, and the remaining cells may become resistant to subsequent chemotherapy. In their study, Nelson and his colleagues found a mechanism by which this happens. The researchers found that cancer cells are surrounded by a type of normal cell (non-tumor cell) called a “fibroblast. They studied a type of normal, non-tumor cell, the fibrous histiocyte, which is found near tumor cells. In animals, fibroblasts help maintain connective tissue, and they are found throughout the body playing a scaffold-like role in stabilizing other cells and tissues. Fibroblasts are also important for wound healing and collagen production. But they behave in unexpected ways in abnormal environments. Nelson and his colleagues studied chemotherapy-treated tumor cells from patients with prostate, breast and ovarian cancers and found that when the DNA of fibroblasts near the tumor was damaged by chemotherapy, they began to release a protein called WNT16B in the tumor microenvironment. protein. They also found that the protein was expressed at high levels – enough to cause cancer cells to grow, invade nearby tissues and become resistant to chemotherapy. They write in the paper that WNT16B expression in the prostate tumor microenvironment diminishes the cytotoxicity of chemotherapy drugs in the body, promotes tumor cell survival, and accelerates cancer pathology. The WNT gene family and proteins are known to be important for the growth of both normal and tumor cells, but this study reveals their role in the phenomenon of treatment resistance. The researchers say that some WNT proteins (expressed) have increased 30-fold, which is, as Nelson says, “simply unpredictable. Tumor treatments are becoming more specific, using precise “sniping” methods to reach key molecules instead of “shotgun” attacks such as damaging DNA. The researchers say their findings suggest that the tumor microenvironment will shape the success or failure of more precise (drug-based) treatments. For example, the same tumor cells, but in different microenvironments, may respond completely differently to the same therapy. They believe their findings could help develop more effective treatments, for example, by finding appropriate ways to block tumor microenvironment responses. Professor Fran Balkwill, a British oncologist who studies the microenvironment, told the press that the study, along with other related research, suggests that tumor treatment is not just about exerting effects on tumor cells, but also focusing on (non-tumor) cells in and around tumor tissue. “Some of the effects are beneficial,” Balkwill said, “for example, the chemotherapy process triggers normal immune cells to attack nearby tumors.” He added, “But this work confirms that normal cells near the tumor can prompt the tumor to become resistant to treatment. The next step is to find ways to target these resistance mechanisms to investigate more effective chemotherapy.”