Lung cancer is the form of cancer that kills most people worldwide – around 1.3 million every year. Almost one fifth of patients receive a diagnosis of small-cell lung cancer, a very aggressive type of tumour that spreads quickly in the body.
“Patients with small-cell lung cancer initially respond well to chemotherapy, but the survival rate is still poor because the majority suffer a relapse within two years and there is then no effective medication available”, explained Matilda Thorén, a doctoral student at the Department of Laboratory Medicine in Malmö, Lund University, who presents the research in her thesis. The results are also the work of researcher Helen Pettersson and Professor Sven Påhlman.
This is where the idea of using an arsenic compound, arsenic trioxide, came from. The use of arsenic in medicine originated from China and it has been used to treat a variety of diseases for thousands of years. In the 1970s, arsenic made a comeback in cancer research, and arsenic trioxide is now used very successfully for treatment of relapses of acute promyelocytic leukaemia (APL).
The thesis shows that arsenic trioxide is just as effective on cultivated small-cell lung cancer as on APL cells, and in trials on mice, cancer growth was drastically curbed in most cases.
“The next step is a clinical study on patients who are no longer responding to chemotherapy. We were planning a clinical study in Lund with lung cancer researchers from Gothenburg. However, the company Cephalon, which has registered arsenic trioxide, has instead chosen to support an American lung cancer study, which nonetheless builds on our results”, said Sven Påhlman, Professor of Molecular Medicine at Lund University.
In two other studies that are included in the thesis, Matilda Thorén has searched for explanations as to why small-cell lung cancer is so resilient and successful in spreading, and she found the results surprising. The cancer turned out not to be dependent on either of the two proteins, HIF-1α and HIF-2α, that normally help cancer tumours to grow in the low-oxygen environment that comes about as a result of the division of the tumour cells. HIF-2α is naturally absent in small-cell lung cancer and for the study, HIF-1α was also removed:
“To our surprise, we found that the cancer cells not only survived in the low-oxygen environment, but that they also continued to divide. This suggests that small-cell lung cancer adapts to a lack of oxygen in a way that is as yet unknown. We are now investigating whether an amino acid, glutamine, plays a part”, said Matilda Thorén.
Matilda Thorén will defend her thesis, Hypoxic Adaptation and Arsenic Trioxide at Lund University on 27 September 2013.
Matilda Thorén, doctoral student, Lund University
+46 46 222 64 40
Sven Påhlman, Professor of Molecular Medicine, Lund University
+46 46 222 64 21, +46 706 38 45 46