HADRON AND PHOTON IRRADIATION COMBINED WITH A CHEMOTHERAPY DRUG: AN IN VITRO STUDY IN HUMAN CANCER CELLS

Nowadays combined therapies exploiting chemotherapy agents and radiation used in conjunction attract a lot of interest, especially when dealing with radio-resistant tumors. In fact, it is known that some drugs have radio-sensitizing effects, for example inhibiting DNA repair mechanisms. The aim of these combined therapies is to obtain better tumor local control and to reduce the risk of distant failures. Many studies with different kind of chemical agents used in combination with photon beams have been performed for different cancers, but at the moment few data about the use of chemicals combined with hadrons are available. The purpose of the study described in this Thesis is the investigation of the interaction of charged hadrons (protons and Carbon ions) or photons and a the chemotherapy agent Epothilone B in human cancer cells cultured in vitro. In particular the study have been performed in lung adenocarcinoma (A549), glioblastoma multiforme (U251MG) and pediatric medulloblastoma (DAOY). Experiments with hadron and photon beams have been performed at the Centro Nazionale di Adroterapia Oncologica (CNAO) in Pavia and at the Istituto nazionale dei Tumori in Milano (IRCCS foundation), respectively. Different biological end-points have been evaluated in irradiated human cancer cells pre-treated or not with Epothilone B: clonogenic survival, cell growth and invasive capacity have been measured. Moreover, in order to evaluate the potential advantages of such a combined therapy, the interaction between radiation and drug has been analyzed to determine whether the interaction mechanism between the two cytotoxic agents is additive or synergic. Epothilone B resulted to act as a radiosensitizer especially with low-LET radiation (photons and protons). Moreover, hadron Relative Biological Effectiveness (RBE) was measured using photon beams as reference radiation, it resulted to be cell line dependent and results are reported in this Thesis.