Resistance of lung cancer cells to chemotherapy decrypted

Causes of chemo-resistance of lung cancer discovered
Lung cancer is one of the most common types of cancer and often the disease, especially in small cell lung carcinoma, discovered only at an advanced stage. Therapeutic options at such a late stage of the disease are still extremely limited, however, especially as the tumors develop resistance to chemotherapy treatment. In a recent study, scientists from MedUni Vienna investigated the cause of this "chemo-resistance" and published their findings in the specialist journals "Cell Adhesion and Migration" and "Trends in Cancer".

Frequently metastases are already present when the diagnosis of a small cell lung carcinoma is made. Here is a chemotherapy (possibly with subsequent radiation treatment), the last hope of those affected. This also shows considerable success on first use, but it is not uncommon "within one year to a tumor recurrence, which no longer reacts to a new chemotherapy," said the MedUni Vienna. The tumor cells develop resistance to the chemotherapeutic agents. The causes of chemo-resistance in small cell lung cancer have now been proven for the first time by researchers led by Gerhard Hamilton from the University Department of Surgery at MedUni Vienna.

Small cell lung cancers are often resistant to chemotherapy. Scientists have now identified the cause of this. (Picture: blueringmedia / fotolia.com)

Threatening recurrence in small cell lung carcinomas
According to the researchers, lung cancer is one of the most common types of cancer in Austria and around 4,000 people die each year as a result of such a disease. "About 85 percent of lung cancers are of the histological type of non-small cell lung carcinoma (NSCLC), which responds fairly well to targeted therapies and immunotherapies," explains MedUni Vienna. The remaining 15 percent of those affected, according to the University of the disease of a small cell lung carcinoma (SCLC), "which consists of neuroendocrine cells and rapidly metastasized." According to findings, usually a cytotoxic chemotherapy followed by radiation. "First, the patients respond to the platinum-based therapy in combination with the active ingredient etoposide very well, but occur within a year resistant tumor recurrence," explain the researchers. In a further therapy with the active ingredients topocetan or anthracyclines then show a low response 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 peculiarity of small cell lung cancer that "many tumor cells migrate into the blood circulation and form metastases as circulating tumor cells." About a year ago, the researchers around Gerhard Hamilton in cooperation with Robert Zeillinger (Molecular Oncology Group, University Hospital for Gynecology) and Maximilian Hochmair (Otto-Wagner Spital) on cultivable tissue cultures of circulating tumor cells show that the individual cells are sensitive to chemotherapeutic agents, but spontaneously form large aggregates, reports MedUni Vienna. These so-called tumor clusters with oxygen-poor core regions are resistant to chemotherapy, because the drugs are difficult to penetrate. In addition, many cells would be in a resting phase due to the lack of oxygen, which makes them insensitive to chemotherapeutic agents. In addition, as a result of the lack of oxygen and the radiation is ineffective, "because the necessary for damaging the tumor cells oxygen radicals are missing," explain the researchers.

New therapeutic approaches required
According to the scientists, the "groundbreaking proof" was "that the chemo and radiation resistance is created by the cluster formation of the circulating tumor cells." Thus, in the first chemotherapy only the main tumor mass is eliminated, but the circulating tumor cells in shape the tumor cluster subsequently lead to recurrence. Therefore, in completely new therapeutic approaches, the formation of the tumor clusters must first be prevented or their dissolution achieved, emphasize Hamilton and colleagues. According to the researchers, their findings may also apply to other malignancies. (Fp)