Resistance of lung cancer cells to chemotherapy drugs decoded

Resistance of lung cancer cells to chemotherapy drugs decoded

Causes of chemo-resistance in lung cancer discovered
Lung cancer is one of the most widespread types of cancer and often the disease, especially in small cell lung cancer, is only discovered at an advanced stage. The treatment options in such a late stage of the disease are still extremely limited, especially since the tumors develop resistance to treatment with chemotherapy. In a current study, scientists at MedUni Vienna examined the cause of this “chemo-resistance” and published their results in the specialist magazines “Cell Adhesion and Migration” and “Trends in Cancer”.

Metastases are often already present when the diagnosis of small cell lung cancer is made. Chemotherapy (possibly followed by radiation treatment) is the last hope of those affected. When used for the first time, this also shows considerable success, but it is not uncommon for “tumor recurrence within one year that no longer reacts to renewed chemotherapy,” according to MedUni Vienna. The tumor cells develop resistance to the chemotherapy drugs. The researchers led by Gerhard Hamilton from the University Clinic for Surgery at the MedUni Vienna have now demonstrated the causes of chemo-resistance in small cell lung cancer for the first time.

Impending recurrence in small cell lung cancer
According to the researchers, lung cancer is one of the most common types of cancer in Austria, where around 4,000 people die each year as a result of such a disease. "Around 85 percent of lung cancers are of the histological type of non-small cell lung cancer (NSCLC), which responds quite well to targeted therapies and immunotherapies," explains the MedUni Vienna. The remaining 15 percent of those affected, according to the university, develop small cell lung cancer (SCLC), "which consists of neuroendocrine cells and rapidly metastasizes." If the findings are correct, cytotoxic chemotherapy with subsequent radiation is usually carried out. "Initially, patients respond very well to platinum-based therapy in combination with the active ingredient etoposide, but resistant tumor recurrences occur within a year," the researchers explain. Further therapy with the active ingredients topocetan or anthracyclines then shows a low response rate to the treatment and survival at this stage is usually only a few months.

Formation of resistant tumor clusters
The scientists describe it as a special feature of small cell lung cancer that "many tumor cells migrate into the blood circulation and form metastases as circulating tumor cells." Around a year ago, the researchers led by Gerhard Hamilton in cooperation with Robert Zeillinger (Molecular Oncology Group, University Clinic for Gynecology) and Maximilian Hochmair (Otto-Wagner Hospital) on cultivable tissue cultures of the circulating tumor cells demonstrate that the individual cells are sensitive to chemotherapy drugs, but can spontaneously form large aggregates, reports the MedUni Vienna. These so-called tumor clusters with oxygen-poor core regions are resistant to chemotherapy because the active ingredients are difficult to penetrate. In addition, many cells would be at rest due to the lack of oxygen, making them insensitive to chemotherapy drugs. In addition, radiation is also ineffective due to the lack of oxygen, "because the oxygen radicals necessary to damage the tumor cells are missing," the researchers explain.

New therapeutic approaches required
According to the scientists, the “groundbreaking proof” was “that the chemo- and radiation resistance arises from the cluster formation of the circulating tumor cells.” Thus, when the chemotherapy was started for the first time, only the main tumor mass was eliminated, but the circulating tumor cells in the form the tumor clusters subsequently lead to relapse. Therefore, the formation of tumor clusters must first be prevented or their resolution achieved in completely new therapeutic approaches, emphasize Hamilton and colleagues. According to the researchers, their findings may also apply to other malignancies. (fp)

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