Several preclinical studies suggested a potential benefit from combined treatment with inhibitors of epidermal growth factor receptor (EGFR) and angiogenesis, both effective in patients with advanced non-small-cell lung cancer (NSCLC). In pretreated patients with advanced EGFR wild type NSCLC, bevacizumab plus erlotinib improved progression-free survival as second-line therapy in the BeTa study and as maintenance therapy in the ATLAS trial, although the benefit was modest and did not translate into an advantage in overall survival. Disappointing results were reported with oral VEGF inhibitors plus erlotinib in pretreated patients with EGFR wild type NSCLC. On the contrary, erlotinib plus bevacizumab or ramucirumab showed a clinically relevant improvement of progression-free survival in naïve patients with EGFR mutations, leading to the approval of these two regimens as first-line treatment of NSCLC patients with EGFR mutant tumors. Several clinical studies are evaluating the feasibility and activity of osimertinib plus bevacizumab or ramucirumab. However, limits that could affect its use in clinical practice are the need of an intravenous infusion for angiogenesis inhibitors, the increased incidence of treatment associated adverse events, the exclusion of patients with tumors located in central position or at risk of hemorrhage. The identification of predictive biomarkers is an important goal of research to optimize the combined use of these agents.

All-trans retinoic acid (ATRA) induces complete remission in a high proportion of acute promyelocytic leukemia (APL). Nevertheless it is be associated with adverse drug reactions that might be life-threatening including differentiation syndrome, myocarditis, myositis, Sweet’s syndrome and ulcers. We describe a case of APL who during induction therapy developed ATRA syndrome, cardiac arrhythmia and multiple episodes of intestinal necrosis that required surgery. In particular, we report here for the first intestinal necrosis attributable to ATRA treatment in the absence of histological evidence of promyelocytes infiltration or leukocytoclastic vasculitis.

Dysregulation of cellular pH is frequent in solid tumours and provides potential opportunities for therapeutic intervention. The acidic microenvironment within a tumour can promote migration, invasion and metastasis of cancer cells through a variety of mechanisms. Pathways associated with the control of intracellular pH that are under consideration for intervention include carbonic anhydrase IX, the monocarboxylate transporters (MCT, MCT1 and MCT4), the vacuolar-type H⁺-ATPase proton pump, and the sodium-hydrogen exchanger 1. This review will describe progress in the development of inhibitors to these targets.