In this study, the main objective is to analyze the effect of genetic variations (polymorphisms) on clinical outcome of colorectal cancer patients treated with oxaliplatin (FOLFOX4 regimen) and those with prostate cancer treated with radiotherapy, with the aim to identify those pharmacogenetic parameters able to provide an indication of a possible "personalization" of therapy. Nanomedicine is the application of nanotechnology in biomedical field to the prevention and treatment of diseases in the human body. Pharmacological research in oncology is aimed at the discovery of new antitumor molecules and especially to improve the use of drugs already present in therapy. In fact, the response to a chemotherapeutic agent is highly variable both in terms of efficacy and tolerability and this may be due both to differences between individuals and molecular characteristics of the tumor. Pharmacogenetics, along with radiogenetics, are concerned to investigate how the genetic characteristics of each individual can influence the therapeutic effect of the drug or radiation and susceptibility to side effects. In particular, they focus on how the constitutive alterations of genetic asset of each individual, so-called polymorphisms, can affect transport, metabolism or the interaction with the target of a drug or treatment. In this study I have investigated the role of genetic polymorphisms, previously identified in the metastatic disease, as predictive markers of neurotoxicity, hematological and non-hematological toxicities from oxaliplatin in colorectal cancer patients treated with adjuvant FOLFOX4 regimen; and I have also identified radiogenetic markers of response in terms of risk of biochemical PSA recurrence and overall survival in prostate cancer patients. In conclusion, the work of this thesis allowed defining new molecular markers that may have prognostic value in the treatment of colorectal cancer with FOLFOX4 regimen and in prostate cancer with radiotherapy. The application of these biomarkers in clinical practice may be useful for designing a personalization of treatment based on specific genetic characteristics of the patients with colorectal cancer and prostate cancer.
