Research / Research Focus / Chemical Safety and Cancer Prevention

Chemical Safety and Cancer Prevention

(Head: Gergely Szakacz, Univ.-Prof. PhD)

Cancer is caused by genomic mutations and tumor-promoting agents that drive malignant transformation and tumor development. Both mechanisms have been linked to environmental factors such as smoking, ultraviolet light or exposure to chemical compounds. The primary focus of the research unit is to elucidate how cancer is induced by environmental carcinogens. According to current estimates, more than half of cancers may be prevented by applying knowledge that we already have! Improved understanding of the complex cellular pathways by which cancer risk factors affect the multistep evolution of cancer will provide further targets for prevention, therapy, and biomarkers of exposure and disease.

Figure showing cancer cells explaining in vitro model studying non-genetic carcinogens:

Figure: To investigate the role of mutagenic and non-genotoxic agents in the development of liver cancer, rat hepatocytes were treated with genotoxic carcinogens, which resulted in single preneoplastic cells (A, in brown), giving rise to large preneoplasia (B). To enable investigations on the molecular and biological alterations associated with the preneoplastic phenotype, we developed an ex-vivo co-culture system for unaltered and initiated hepatocytes (C). In these models we identify non-genotoxic carcinogens that promote the outgrowth of initiated hepatocytes, and to test chemopreventive agents interfering with this process. (click to enlarge)

Progress in the prevention, early diagnosis, and treatment of cancer has led to a steady decline in cancer death rates. Still, despite significant progress, resistance to anticancer therapy is the main reason why cancer remains a deadly disease. Another aim is to elucidate the molecular basis of therapy resistance that may occur through selection, the acquisition of new mutations or the adaptation of cancer cells to treatment. Profiling tumors in different stages of therapy can identify vulnerabilities that may be exploited therapeutically. Effective targeting of the adaptive process will result in a paradigm shift, changing the focus from countering drug resistance mechanisms to preventing therapy resistance.