This study was performed to investigate the role of 68 Ga-DOTANOC SUV max as a potential prognostic factor in patients with pancreatic neuroendocrine tumor (pNET). Methods: Among the patients who underwent 68 Ga-DOTANOC PET/CT, we retrospectively collected the data of those who had G1 or G2 pNET (2010 World Health Organization classification), presented with disease on PET/CT and CT, and had at least 6 mo of follow-up. Patients with multiple endocrine neoplasia were excluded. Results: Overall, 43 patients were included. No significant differences in SUV max were observed with respect to sex, tumor syndrome, stage, World Health Organization classification, or Ki-67. During follow-up (median, 20 mo), 11 patients (35.6%; median, 33 mo; interquartile range, 20-48 mo) had stable disease and 32 (74.4%; median, 19 mo; interquartile range, 14-26 mo) had progressive disease. SUV max at 24 mo of follow-up was significantly higher (P 5 0.022) in patients with stable disease than in patients with progressive disease. The best SUV max cutoff ranged from 37.8 to 38.0. The major risk factors for progression included an SUV max of no more than 37.8 (hazard ratio, 3.09; P 5 0.003), a Ki-67 of more than 5% (hazard ratio, 2.89; P 5 0.009), and medical therapy alone (hazard ratio, 2.36; P 5 0.018). Advanced stage (IV) (P 5 0.026), an SUV max of less than 37.8 (P 5 0.043), and medical therapy alone (P 5 0.015) were also confirmed at multivariate analysis. Median progression-free survival was 23 mo. Significant differences in progression-free survival were observed in relationship to Ki-67 (median, 45 mo for Ki-67 # 5% and 20 mo for Ki-67 . 5%; P 5 0.005), SUV max (,37.8 vs. .38.0: 16.0 vs. 27.0 mo; P 5 0.002), and type of therapy (medical vs. peptide receptor radionuclide therapy: 16.0 vs. 26.0 mo; P 5 0.014). Conclusion: 68 Ga-DOTANOC SUV max is a relevant prognostic factor in patients with G1 and G2 pNET, and its routine use will improve disease characterization and management in these patients, who may present with atypical cases showing heterogeneous clinical behavior.

The mechanistic target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AkT)/mTOR pathway and owes its name to the inhibitory effect of rapamycin. The mTOR has a central converging role for many cell functions, serving as a sensor for extracellular signals from energy status and nutrients availability, growth factors, oxygen and stress. Thus, it also modulates switch to anabolic processes (protein and lipid synthesis) and autophagy, in order to regulate cell growth and proliferation. Given its functions in the cell, its deregulation is implicated in many human diseases, including cancer. Its predominant role in tumorigenesis and progression of neuroendocrine tumors (NETs), in particular, has been demonstrated in preclinical studies and late clinical trials. mTOR inhibition by everolimus is an established therapeutic target in NETs, but there are no identified predictive or prognostic factors. This review is focused on the role of mTOR and everolimus in NETs, from preclinical studies to major clinical trials, and future perspectives involving mTOR in the treatment of NETs.

Abstract:In recent years, the study of genomic alterations and protein expression involved in the pathways of breast cancer carcinogenesis has provided an increasing number of targets for drugs development in the setting of metastatic breast cancer (i.e., trastuzumab, everolimus, palbociclib, etc.) significantly improving the prognosis of this disease. These drugs target specific molecular abnormalities that confer a survival advantage to cancer cells. On these bases, emerging evidence from clinical trials provided increasing proof that the genetic landscape of any tumor may dictate its sensitivity or resistance profile to specific agents and some studies have already showed that tumors treated with therapies matched with their molecular alterations obtain higher objective response rates and longer survival. Predictive molecular biomarkers may optimize the selection of effective therapies, thus reducing treatment costs and side effects. This review offers an overview of the main molecular pathways involved in breast carcinogenesis, the targeted therapies developed to inhibit these pathways, the principal mechanisms of resistance and, finally, the molecular biomarkers that, to date, are demonstrated in clinical trials to predict response/resistance to targeted treatments in metastatic breast cancer.

Pancreatic ductal adenocarcinoma cancer (PDAC) is the fourth leading cause of cancer death worldwide. Recently, two chemotherapy regimens have proven to improve median overall survival in comparison with gemcitabine. Based on better understanding of tumor molecular biology and of the role of tumor microenvironment, monoclonal antibodies (mAbs) could be an interesting and new type of targeted treatment of PDAC. Areas covered: Preclinical and clinical trials have evaluated the efficacy of several mAbs in pancreatic cancer treatment. This review will underline the most important targeted pathways by mAbs involved in this disease, including EGFR, HER-2, IGF-1 R, VEGF/VEGFR, NOTCH, WNT and immune checkpoints. Expert opinion: Despite the promising results of preclinical and phase I trials, the addition of mAbs to standard chemotherapy or in association with other target agents seems not to confirm these results in the following phase II and III trials in pancreatic cancer patients. However, an improved patient selection before treatment based on molecular characteristics in association with reliable predictive biomarkers can identified more efficacious treatment approaches, minimizing toxicity profile of these drugs.