Introduction: There is general agreement that increased angiogenesis is an important factor in determining prostate cancer development and prognosis. Vascular Endothelial Growth Factor (VEGF) is thought to play a primary role in the molecular events that lead to prostate cancer progression, from androgen-dependency to castration-resistance until dissemination to the skeleton. Bevacizumab is a recombinant anti-VEGF monoclonal antibody that has exhibited clinical activity in different cancer types.Areas covered: In this review we summarize the data of clinical trials, investigating the effects of bevacizumab in prostate cancer patients. Until now, the drug has demonstrated anti-tumoral activity although with no improvements in overall survival (OS) and a wide range of alarming side effects in metastatic castration-resistant prostate cancer (mCRPC). Recently, promising results were achieved, using bevacizumab in combination with androgen deprivation therapy (ADT) in patients with recurrent prostate cancer after definitive local therapy.Expert opinion: The suboptimal efficacy of bevacizumab may relate to molecular events triggered during disease progression, such as redundancy of angiogenic factors or the interfering influence of androgens on angiogenic pathways. Further studies, using bevacizumab in combination with ADT and/or inhibitors of other key pathways on the subset of patients with low burden, hormone sensitive prostate cancer, need to be conducted.

Advances in clinical research have led to official approval of several new treatments for metastatic prostate cancer in the last three years: sipuleucel-T, cabazitaxel, abiraterone acetate, radium-223 and enzalutamide. Although these agents have all been shown to improve overall survival in randomized Phase III trials, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. First, the review summarizes the current literature on the biology of mCRPC. The emerging data are increasing our understanding of the mechanisms that underlie the pathogenesis of castrate resistance and where future treatment might be headed. In the second part of the review, the authors assess the future directions in disease therapy. Indeed, novel selected therapeutic approaches, including novel agents and combinatorial therapies, are showing promising early results. Targeting different molecular pathways in combination with immunotherapy can be a promising direction in metastatic castration prostate cancer treatment. However, several challenges still exist including elucidating the optimal use and sequencing of these new agents. There are also challenges in both the design and the interpretation of the results from clinical trials.

Pancreatic cancer is a challenging disease with limited treatment options and a high mortality rate. Just few therapy advances have been made in recent years. Tumor microenvironment, immunosuppressive features and mutational status represent important obstacles in the improvement of survival outcomes. Up to now, first-line therapy did achieve a median overall survival of less than 12 months and this discouraging data lead clinicians all over the world to focus their efforts on various fields of investigation: 1) sequential cycling of different systemic therapy in order to overcome mechanisms of resistance; 2) discovery of new predictive bio-markers, in order to target specific patient population; 3) combination treatment, in order to modulate the tumor microenvironment of pancreatic cancer; 4) new modalities of the delivery of drugs in order to pass the physical barrier of desmoplasia and tumor stroma. This review shows future directions of treatment strategies in advanced pancreatic cancer through a deep analysis of these recent macro areas of research.

Breast cancer is a complex and highly heterogeneous disease consisting of various subtypes. It is classified into human epidermal growth receptor 2 (HER-2)-enriched, luminal A, luminal B and basal-like/triple negative (TNBC) breast cancer, based on histological and molecular features. At present, clinical decision-making in breast cancer is focused only on the assessment of tumor cells; nevertheless, it has been recognized that the tumor microenvironment (TME) plays a critical biologic role in breast cancer. This is constituted by a large group of immune and non-immune cells, but also by non-cellular components, such as several cytokines. TME is deeply involved in angiogenesis, immune-evasion strategies, and propensity for early metastatic spread, impacting on prognosis and prediction of response to specific treatments. In this review, we focused our attention on the early morphological changes of tumor microenvironment (tumor vasculature features, presence of immune and non-immune cells infiltrating the stroma, levels of cytokines) during breast cancer development. At the same time, we correlate these characteristics with early metastatic propensity (defined as synchronous metastasis or early recurrence) with particular attention to breast cancer subtypes.

Introduction: Despite the emergence of several new effective treatments for metastatic castration-resistant prostate cancer patients, disease progression inevitably occurs, leading scientific community to carefully look for novel therapeutic targets of prostate cancer. Kallikrein (KLK)-related peptidases have been demonstrated to facilitate prostate tumorigenesis and disease progression through the development of an oncogenic nnicroenvironnnent for prostate cells. Areas covered: This review first summarizes the large amount of preclinical data showing the involvement of KLKs in prostate cancer pathobiology. In the second part, the authors assess the current status and future directions for KLK-targeted therapy and briefly describe the advances and challenges implicated in the design of effective manufactured drugs. The authors then focus on the preclinical data and on Phase I/II studies of the most promising KLK-targeted agents in prostate cancer. The drugs discussed here are divided on the basis of their mechanism of action: KLK-engineered inhibitors; KLK-activated pro-drugs; KLK-targeted microRNAs and small interfering RNAs(-/-)small hairpin RNAs; KLK vaccines and antibodies. Expert opinion: Targeting KLK expression and/or activity could be a promising direction in prostate cancer treatment. Future human clinical trials will help us to evaluate the real benefits, toxicities and the consequent optimal use of KLK-targeted drugs, as mono-therapy or in combination regimens.