2,971 publications from this institution
Abstract Most tumors display oncogene-driven reprogramming of several metabolic pathways, which are crucial to sustain their growth and proliferation. In recent years, both dietary and pharmacologic approaches that target deregulated tumor metabolism are beginning to be considered for clinical applications. Dietary interventions exploit the ability of nutrient-restricted conditions to exert broad biological effects, protecting normal cells, organs, and systems, while sensitizing a wide variety of cancer cells to cytotoxic therapies. On the other hand, drugs targeting enzymes or metabolites of crucial metabolic pathways can be highly specific and effective, but must be matched with a responsive tumor, which might rapidly adapt. In this review, we illustrate how dietary and pharmacologic therapies differ in their effect on tumor growth, proliferation, and metabolism and discuss the available preclinical and clinical evidence in favor of or against each of them. We also indicate, when appropriate, how to optimize future investigations on metabolic therapies on the basis of tumor- and patient-related characteristics. Significance: To our knowledge, this is the first review article that comprehensively analyzes the preclinical and preliminary clinical experimental foundations of both dietary and pharmacologic metabolic interventions in cancer therapy. Among several promising therapies, we propose treatment personalization on the basis of tumor genetics, tumor metabolism, and patient systemic metabolism.Cancer Discov; 6(12); 1315–33. ©2016 AACR.
To compare the separate and combined effects of alcohol drinking and smoking between the 2 sites, we evaluated 274 men with oral cancer, 364 with pharyngeal cancer and 1,254 controls, frequency-matched for age and area of residence, from Italy and Switzerland. Extremely elevated risk increases for oral cancer (odds ratio, OR = 228) and pharyngeal cancer (OR = 100) were found for the highest joint level of drinking (≥77 drinks/week) and smoking (≥25 cigarettes/day). Ratios of ORs between oral cancer and pharyngeal cancer vs. controls, obtained by polytomous logistic regression, suggested that the risk increase for oral cancer was about 2-fold greater than that for pharyngeal cancer at each combined level of smoking and drinking, except at low levels of drinking in smokers. A clear departure from risk difference additivity was present for both oral and pharyngeal cancer in individuals heavily exposed to both factors versus non-smoking abstainers/light drinkers. Our findings thus help explain observations from descriptive epidemiology that, if smoking level in a population does not change substantially, but alcohol consumption increases, increase in oral cancer would be greater than at any other site in the upper aero-digestive tract, including cancer of the pharynx. Int. J. Cancer 83: 1–4, 1999. © 1999 Wiley-Liss, Inc.
Peptic ulcer and gastrectomy are associated with an increased risk of oesophageal cancer. We considered the relation between treatment with histamine-2 (H-2)-receptor antagonists and subsequent risk of oesophageal cancer. Data from a case-control study conducted between 1984 and 1995 in northern Italy were used. These comprised 407 incident, histologically confirmed cases and 1168 controls admitted for acute, non-neoplastic, non-digestive tract conditions, unrelated to known risk factors for oesophageal cancer. Ten (2.5%) cases and 52 (4.5%) controls reported using H-2-receptor antagonists at some time, corresponding to a multivariate odds ratio (OR) of 0.5 (95% confidence interval 0.2-1.0). The OR was 0.4 for subjects who had started use seven years earlier or less, and 0.6 for those who had started use more than seven years ago. These findings indicate that risk of oesophageal cancer is not increased among H-2-receptor antagonist users. This trend to protection may be explained in terms of chance alone, or may be partly related to a possible favourable impact of H-2-receptor-antagonists on chronic oesophageal carcinogenesis.
The relationship between spontaneous and induced abortions and breast cancer risk was analyzed using data from a case-control study conducted between June 1991 and February 1994 in 6 Italian centers on 2,569 histologically confirmed incident breast cancer cases and 2,588 controls admitted to hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases. One or more abortions were reported by 31% of cases and 32% of controls, corresponding to a multivariate odds ratio (OR) of 1.0 (95% confidence interval [CI], 0.8–1.1). No trend in risk was observed with increasing number of total abortions or spontaneous and induced abortions separately. No significant relationship was found between the risk of breast cancer and history of spontaneous or induced or total abortions in separate strata of age at diagnosis, number of children, time of abortion in relation to first birth and family history of breast cancer. When abortion was the outcome of the first pregnancy, the OR was 1.2 for spontaneous and 1.3 for induced abortion, in relation to women with birth as outcome of the first pregnancy, and 1.0 and 1.1, respectively, when the reference category was nulligravidae. Thus, our results indicate a lack of association between induced and spontaneous abortions and breast cancer risk. © 1996 Wiley-Liss, Inc.
