Diagnosis, Management and Theragnostic Approach of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms.

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) constitute an ideal target for radiolabeled somatostatin analogs. The theragnostic approach is able to combine diagnosis and therapy by the identification of a molecular target that can be diagnosed and treated with the same radiolabeled compound. During the last years, advances in functional imaging with the introduction of somatostatin analogs and peptide receptor radionuclide therapy, have improved the diagnosis and treatment of GEP-NENs. Moreover, PET/CT imaging with 18F-FDG represents a complementary tool for prognostic evaluation of patients with GEP-NENs. In the field of personalized medicine, the theragnostic approach has emerged as a promising tool in diagnosis and management of patients with GEP-NENs. The aim of this review is to summarize the current evidence on diagnosis and management of patients with GEP-NENs, focusing on the theragnostic approach.

Non-invasive detection of epithelial mesenchymal transition phenotype and metastatic dissemination of lung cancer by liquid biopsy.

The occurrence of phenotype switch from an epithelial to a mesenchymal cell state during the activation of the epithelial mesenchymal transition (EMT) program in cancer cells has been closely associated with the generation of invasive tumor cells that contribute to metastatic dissemination and treatment failure. Liquid biopsy represents an emergent non-invasive tool that may improve our understanding of the molecular events leading to cancer progression and initiating the metastatic cascade through the dynamic analysis of tumor-derived components isolated from body fluids. The present review will primarily focus on the applications of liquid biopsy in lung cancer patients for identifying EMT signature, elucidating molecular mechanisms underlying the acquisition of an invasive phenotype and detecting new targets for therapy.

Functional imaging of multidrug resistance in breast cancer.

Intrinsic or acquired multidrug resistance is the major cause of treatment failure in many human cancers. Multiple cellular mechanisms may contribute to the development of multidrug resistance including overexpression of P-glycoprotein (Pgp). The use of 99mTc-labeled lipophilic cations, which are transport substrate of Pgp, raised the possibility to predict the tumor response to treatment and to identify patients who will become refractory to subsequent therapy. Among these agents, 99mTc-MIBI is the most widely evaluated tracer and may serve as a paradigm of this class of compounds. In particular, many studies have shown the prognostic value of 99mTc-MIBI scan in different types of malignancy including breast cancer and the correlation with the expression of Pgp. However, additional mechanisms of cell resistance, mainly involving alterations of apoptosis, may also affect 99mTc-MIBI uptake in tumors. In particular, overexpression of the anti-apoptotic protein Bcl-2 prevents tumor cells to enter apoptosis and inhibits tracer accumulation into mitochondria. Therefore, while an absent or reduced early tracer uptake in large breast carcinomas reflects the existence of a defective apoptotic program, an enhanced tracer clearance in 99mTc-MIBI positive lesions reflects the activity of drug transporters such as Pgp. The existence of two different mechanisms underlying the predictive role of 99mTc-MIBI scan may be important to establish whether individual patients may benefit from Pgp inhibitors or Bcl-2 antagonists.