DEVELOPMENT OF A NEW FAST CHEMOSENSITIVITY TEST FOR CANCER

Cancer treatment is currently empirical. Evidence of genetic, molecular cell pathology and clinical studies suggests that the same tumour in different patients shows different chemosensitivity results indeed. Actually, even many chemotherapeutic agents and the ultimate pharmacological strategies, disease progression and patient death are still a problem because of clinical drug resistance. It would be useful to test selected anticancer drugs individually and predict the effect of chemotherapy on each tumour by drug sensitivity testing, in order to achieve a higher response rate. Various types of in vitro tests, based on histoculture or cell culture techniques have been developed over the past five decades. However none of these tests have been applied clinically and no standard method has been established yet. The aim of the present research project is to perform a new, easy, accurate and fast method, in which tumour samples from human malignant tumor are directly exposed, for a short period, to multiple chemotherapeutic drugs. The main objectives of this study were: characterize the morphological changes induced in tumour specimens by chemotherapeutic agents, determine effects of anticancer drugs on molecular markers involved in proliferation and/or apoptosis, and correlate the observed in vitro results with the clinical outcome of each patient. Extracellular and/or intracellular oedema, apoptosis and necrosis were the morphological modifications in cisplatin-treated specimens from malignant tumor. Any morphological change was revealed in normal tissue and benign lesion following cisplatin exposure. The reactivity for p53 showed the most relevant results among the immunohistochemical markers correlated to cell proliferation and apoptosis. In squamous cell carcinoma from larynx and oral cavity p53 immunoreactivity for p53 can change in vitro either after cisplatin exposure and after docetaxel exposure; less relevant results were observed with 5-flurouracil exposure. The p53 reactivity change is different with different chemotherapeutic agents. The relationship between p53 overexpression and decrease and the chemotherapeutic agents’ mechanism of action is the central thesis of the study.