Angiogenesis in pancreatic ductal adenocarcinoma: A controversial issue

Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early loco-regional spread and distant metastases at diagnosis, leading to dismal prognosis with a 5-year overall survival rate moderately over than 5%. This malignancy is largely resistant to chemotherapy and radiation, but the reasons of the refractoriness to the therapies is still unknown. Evidence is accumulating to indicate that the PDAC microenvironment and vascularity strongly contribute to the clinical features of this disease. In particular, PDAC is characterized by excessive dense extracellular matrix deposition associated to vasculature collapse and hypoxia with low drug delivery, explaining at least partly the low efficacy of antiangiogenic drugs in this cancer. Strategies aimed to modulate tumor stroma favoring vasculature perfusion and chemotherapeutics delivery are under investigation

Emerging role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standardcare for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results inan alternative first-line treatment for the Chineseclinical oncology guidelines. Moreover,nivolumab and pembrolizumab,two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approvedfor subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessmentof new ICIs-based combinatory approaches

Immune system and bone microenvironment: rationale for targeted cancer therapies

Osteoimmunology was coined about twenty years ago to identify a strict cross talk between bone niche and immune system both in physiological and pathological activities, including cancer. Several molecules are involved in the complex interaction between bone niche, immune and cancer cells. The Receptor Activator of NF-kB (RANK)/RANK Ligand (RANKL/Osteoprotegerin (OPG) pathway plays a crucial role in bone cells/cancer interactions with subsequently immune system control failure, bone destruction, inhibition of effect and metastasis outcome. The bidirectional cross talk between bone and immune system could became a potential target for anticancer drugs. Several studies evidenced a direct anticancer role with improved survival of bone-targeted therapies such as bisphosphonates and RANKL antagonist Denosumab. Conversely, initial data evidenced a possible anti-bone resorption effect of systemic anticancer drugs through and immunomodulation activity, i.e. new generation antiandrogens (Abiraterone) in prostate cancer. All data could open a future rationale of combined bone, immunologic and targeted therapies in cancer treatment

Targeting angiogenesis in biliary tract cancers: An open option

Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and evidenced that aberrations in several genes enrolled in the pro-angiogenic signaling, such as FGF receptor-2 (FGFR-2), are characteristic of BTCs. New drugs targeting the signaling pathways involved in angiogenesis have been tested in preclinical studies both in vitro and in vivo with promising results. Moreover, several clinical studies tested monoclonal antibodies against VEGF and tyrosine kinase inhibitors targeting the VEGF and the MEK/ERK pathways. Herein, we evaluate both the pathogenic mechanisms of BTCs focused on angiogenesis and the preclinical and clinical data available regarding the use of new anti-angiogenic drugs in these malignancies

Bonifica dei terreni contaminati. Osservazioni critiche, linee guida e proposte normative

Una delle tematiche legate alla tutela dell'ambiente che oggi richiede maggiore attenzione è quella dei terreni contaminati per la quale è sentita la necessità di un aggiornamento del quadro normativo. Il Tavolo di Roma, un think tank costituitosi alcuni anni fa per una gestione sostenibile dei rifiuti e delle risorse, composto da figure professionali non portatrici di interessi, in rappresentanza di diversi ambiti disciplinari e funzionali, si è fatto interprete di questa esigenza, promuovendo la costituzione del Comitato Tecnico Terreni Contaminati (CTTC). L'apporto di diversi ambiti disciplinari ha determinato, grazie anche a un intenso e franco confronto sempre condotto con logiche tecnico-scientifiche, un fermento di idee e una varietà di osservazioni che costituiranno il migliore viatico per una revisione della normativa fondata saldamente su un elevato grado di accettazione e di condivisione da parte della comunità coinvolta nella sua applicazione

Bonifica dei Terreni Contaminati. Osservazioni critiche, linee guida e proposte normative.

Una delle tematiche legate alla tutela dell'ambiente che oggi richiede maggiore attenzione è quella dei terreni contaminati per la quale è da tutti sentita la necessità di un aggiornamento del quadro normativo. Il Tavolo di Roma, un think tank costituitosi alcuni anni fa per una gestione sostenibile dei rifiuti e delle risorse, composto da figure professionali non portatrici di interessi, in rappresentanza di diversi ambiti disciplinari e funzionali, si è fatto interprete di questa esigenza, promuovendo la costituzione del Comitato Tecnico Terreni Contaminati (CTTC). L'apporto dei diversi ambiti disciplinari ha determinato, grazie anche a un intenso e franco confronto sempre condotto con logiche tecnico-scientifiche, un fermento di idee e una varietà di osservazioni che costituiranno il migliore viatico per una revisione della normativa fondata saldamente su un elevato grado di accettazione e di condivisione da parte della comunità coinvolta nella sua applicazione