Pharmaceutical marketing: its effects on drug sales and beyond

PhD ceremony: Ms. R.R. Ruela de Sousa, 11.00 uur, Doopsgezinde Kerk, Oude Boteringestraat 33, Groningen

Dissertation: New approaches to overcome cancer cell resistance and survival

Promotor(s): prof. M.P. Peppelenbosch

Faculty: Medical Sciences

Despite the progress in understanding the pathogenesis of cancer, for many patients there is still no effective therapy available. In addition, the development of resistance to tumour therapy may lead to major problems. Thus, studies about molecular mechanisms of carcinogenesis, chemo resistance acquisition and cell death induction can contribute largely to cancer therapy. In this thesis it was demonstrated that the Hedgehog protein plays an important role in leukemic cell resistance and the inhibition of this protein increases the sensitivity of leukemic cells to chemotherapy. Furthermore, treatment of tumours with natural compounds from vegetables, fruits and plants was studied. Fisetin, apigenin and ferruginol are able to inhibit tumour cell growth by blocking the cell cycle and induction of programmed cell death. Although the molecular mechanisms responsible for each substance are different, the phosphatases seems to play a role. This is a family of proteins whose importance in cancer has so far been neglected. Although the use of natural substances in the treatment of various tumours appears promising, there may also be downsides. For example, apigenin impaired the efficiency of vincristine, a widely used chemotherapy drug, in some leukemic cells.