Browsing by Author "Di Nunno, Vincenzo"

Now showing 1 - 9 of 9
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    Adjuvant therapy in renal cell carcinoma: is it the right strategy to inhibit VEGF?
    (AME Publishing, 2021-03) Mollica, Veronica; Rizzo, Alessandro; Di Nunno, Vincenzo; Santoni, Matteo; Cheng, Liang; Lopez-Beltran, Antonio; Scarpelli, Marina; Cimadamore, Alessia; Montironi, Rodolfo; Massari, Francesco; Pathology and Laboratory Medicine, School of Medicine
    Despite several clinical trials have assessed different agents in the adjuvant setting, renal cell carcinoma (RCC) still remains a disease orphan of an effective adjuvant treatment. In fact, systemic therapies targeting angiogenesis that have been observed to be effective in metastatic setting failed to show an improvement in terms of clinical outcomes when used ad adjuvant treatments. In this study, we performed a meta-analysis of 5 randomized clinical trials to assess the impact of tyrosine kinase inhibitors (TKIs) targeting angiogenesis after surgery: ASSURE, S-TRAC, PROTECT, ATLAS, SORCE. Among the 6,531 patients assessed, we confirmed the lack of efficacy of adjuvant treatments in terms of disease-free survival (DFS) (pooled-HR 0.93, 95% CI, 0.84–1.02, P=0.16) and overall survival (OS) (pooled-HR 0.98, 95% CI, 0.88–1.09, P=0.54). To the best of our knowledge, we still ignore why some treatments active in the metastatic setting do not show similar efficacy as adjuvant treatment. Exploring possible reasons of this apparently conflicting results is important as it may offer new insights that should be evaluated in next generation adjuvant trials. Immune checkpoint inhibitors (ICIs) have reported significant results—as monotherapy or in combinations with other anticancer agents—in metastatic setting, and the results of trials evaluating these agents in the adjuvant setting are awaited.
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    Another one in the chamber: cabozantinib for patients with metastatic non clear cell renal cell carcinoma
    (AME Publishing Company, 2019-07) Di Nunno, Vincenzo; Massari, Francesco; Mollica, Veronica; Cimadamore, Alessia; Santoni, Matteo; Cheng, Liang; Lopez-Beltran, Antonio; Scarpelli, Marina; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
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    The Human Microbiota and Prostate Cancer: Friend or Foe?
    (MDPI, 2019-03-31) Massari, Francesco; Mollica, Veronica; Di Nunno, Vincenzo; Gatto, Lidia; Santoni, Matteo; Scarpelli, Marina; Cimadamore, Alessia; Lopez-Beltran, Antonio; Cheng, Liang; Battelli, Nicola; Montironi, Rodolfo; Brandi, Giovanni; Pathology and Laboratory Medicine, School of Medicine
    The human microbiome is gaining increasing attention in the medical community, as knowledge on its role not only in health but also in disease development and response to therapies is expanding. Furthermore, the connection between the microbiota and cancer, especially the link between the gut microbiota and gastrointestinal tumors, is becoming clearer. The interaction between the microbiota and the response to chemotherapies and, more recently, to immunotherapy has been widely studied, and a connection between a peculiar type of microbiota and a better response to these therapies and a different incidence in toxicities has been hypothesized. As knowledge on the gut microbiota increases, interest in the residing microbial population in other systems of our body is also increasing. Consequently, the urinary microbiota is under evaluation for its possible implications in genitourinary diseases, including cancer. Prostate cancer is the most common cancer in the male population; thus, research regarding its etiology and possible factors correlated to disease progression or the response to specific therapies is thriving. This review has the purpose to recollect the current knowledge on the relationship between the human microbiota and prostate cancer.
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    Immune checkpoint inhibitors for metastatic bladder cancer
    (Elsevier, 2018-03) Massari, Francesco; Di Nunno, Vincenzo; Cubelli, Marta; Santoni, Matteo; Fiorentino, Michelangelo; Montironi, Rodolfo; Cheng, Liang; Lopez-Beltran, Antonio; Battelli, Nicola; Ardizzoni, Andrea; Pathology and Laboratory Medicine, School of Medicine
    Chemotherapy has represented the standard therapy for unresectable or metastatic urothelial carcinoma for more than 20 years. The growing knowledge of the interaction between tumour and immune system has led to the advent of new classes of drugs, the immune-checkpoints inhibitors, which are intended to change the current scenario. To date, immunotherapy is able to improve the overall responses and survival. Moreover, thanks to its safety profile immune-checkpoint inhibitors could be proposed also to patients unfit for standard chemotherapy. No doubts that these agents have started a revolution expected for years, but despite this encouraging results it appears clear that not all subjects respond to these agents and requiring the development of reliable predictive response factors able to isolate patients who can more benefit from these treatments as well as new strategies aimed to improve immunotherapy clinical outcome. In this review we describe the active or ongoing clinical trials involving Programmed Death Ligand 1 (PD-L1), Programmed Death receptor 1 (PD-1) and Cytotoxic-T Lymphocyte Antigen 4 (CTLA 4) inhibitors in urothelial carcinoma focusing our attention on the developing new immune-agents and combination strategies with immune-checkpoint inhibitors.
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    Immunotherapy in renal cell carcinoma: latest evidence and clinical implications
    (Just Medical Media, 2018-06-05) Santoni, Matteo; Massari, Francesco; Di Nunno, Vincenzo; Conti, Alessandro; Cimadamore, Alessia; Scarpelli, Marina; Montironi, Rodolfo; Cheng, Liang; Battelli, Nicola; Lopez-Beltran, Antonio; Pathology and Laboratory Medicine, School of Medicine
    Advances in understanding the mechanisms of tumour-induced immunosuppression have led to the development of immune-checkpoint inhibitors in cancer patients, including those with renal cell carcinoma (RCC). The optimal combination between immunotherapy and targeted agents (as well as the possible favourable sequential therapy of these two classes of drugs) remains an open question at this moment. Several trials are currently underway to assess the combination of anti-programmed-death 1 (PD-1) or anti-PD-ligand(L)1 agents with other immunotherapies or with anti-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). In this editorial, we described the results of the most recent clinical trials on the use of immunotherapies in RCC and the emerging data on the research for reliable biomarkers of tumour response in this setting. In addition, we have focused on the role of the gut microbiome and tumour microenvironment in the development of future therapeutic strategies for RCC patients.
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    Key Role of Obesity in Genitourinary Tumors with Emphasis on Urothelial and Prostate Cancers
    (MDPI, 2019-08-22) Santoni, Matteo; Cimadamore, Alessia; Massari, Francesco; Piva, Francesco; Aurilio, Gaetano; Martignetti, Angelo; Scarpelli, Marina; Di Nunno, Vincenzo; Gatto, Lidia; Battelli, Nicola; Cheng, Liang; Lopez-Beltran, Antonio; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
    Background: In human populations, a certain amount of data correlate obesity/body mass index (BMI) with urothelial cancer (UC) and prostate cancer (PCa) occurrence, however this is not fully elucidated at all stages of disease. In an attempt to shed light on uncertain areas in such field, in the present review we illustrate the main molecular mechanisms linking obesity and cancer, focusing on the correlation between obesity and tumor risk, disease progression and response to chemo- and immunotherapy in patients with UC and the predictive/prognostic role of obesity in PCa patients treated with the currently available therapeutic approaches. Methods: We did a large-scale literature search on existing scientific websites focusing on keywords "obesity", "body mass index (BMI)", "urothelial cancer", "prostate cancer", "docetaxel", "cabazitaxel", "abiraterone acetate", "enzalutamide", and "radium223". Results: Many adipocytes-induced molecules support tumor proliferation through activation of various cellular pathways. The available evidence in the postoperative setting do the role of BMI in oncological outcomes prediction still not completely clear. Likewise, in metastatic UC patients controversial results link the role of obesity/BMI with clinical outcomes of tumor response to chemotherapy. Adipose stromal cells recruitment, induced by PCa cells, from white adipose tissue to the tumor sites inducing cell invasiveness was associated with poor survival. Conflicting data, although more oriented towards a better survival outcome, resulted in obese patients treated with docetaxel. In PCa cell-lines a certain cabazitaxel chemo resistance adipose stromal cells (ASC)-mediated was demonstrated. In metastatic castration-resistant PCa patients with high BMI (>25 kg/m2) receiving abiraterone acetate there were significant worse survival outcomes, while in enzalutamide patients BMI did not affect survival outcome. In radium 223 patients higher BMI significantly correlated with favorable overall survival. Conclusions: The main focus of this review was to understand the interplay between obesity/BMI and UC/PCa. Several pathogenic cellular pathways exploring the issue are discussed, opening the way to challenging tailored treatments on the basis of BMI. Improving the knowledge of molecular connections between obesity and UC and PCa could favor the development of new therapies likely reducing chemo- and immunotherapy drug resistance.
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    Molecular Mechanisms Related to Hormone Inhibition Resistance in Prostate Cancer
    (MDPI, 2019-01-11) Mollica, Veronica; Di Nunno, Vincenzo; Cimadamore, Alessia; Lopez-Beltran, Antonio; Cheng, Liang; Santoni, Matteo; Scarpelli, Marina; Montironi, Rodolfo; Massari, Francesco; Pathology and Laboratory Medicine, School of Medicine
    Management of metastatic or advanced prostate cancer has acquired several therapeutic approaches that have drastically changed the course of the disease. In particular due to the high sensitivity of prostate cancer cells to hormone depletion, several agents able to inhibit hormone production or binding to nuclear receptor have been evaluated and adopted in clinical practice. However, despite several hormonal treatments being available nowadays for the management of advanced or metastatic prostate cancer, the natural history of the disease leads inexorably to the development of resistance to hormone inhibition. Findings regarding the mechanisms that drive this process are of particular and increasing interest as these are potentially related to the identification of new targetable pathways and to the development of new drugs able to improve our patients' clinical outcomes.
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    Recent Advances in Liquid Biopsy in Patients With Castration Resistant Prostate Cancer
    (Frontiers, 2018-09-24) Di Nunno, Vincenzo; Gatto, Lidia; Santoni, Matteo; Cimadamore, Alessia; Lopez-Beltran, Antonio; Cheng, Liang; Scarpelli, Marina; Montironi, Rodolfo; Massari, Francesco; Pathology and Laboratory Medicine, School of Medicine
    Management of localized and advanced prostate cancer benefits from several therapeutic options with a surprising improvement in terms of clinical outcome. The selection of patients more likely to benefit from a specific approach still remains a key issue as well as the early identification of patients with aggressive disease which could benefit from a more aggressive treatment strategy. The lack of reliable bio-marker in castration resistant setting able to monitor response to treatment and early inform about tumor progression is an emerging issue. Accordingly, circulating DNA and circulating tumor cells appears a promising and attractive approach despite to date practical applications of these techniques are few and not validated. The aim of this review of the literature is to explore current knowledge on liquid biopsy in prostate cancer focusing on possible future applications.
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    Resistance to Systemic Agents in Renal Cell Carcinoma Predict and Overcome Genomic Strategies Adopted by Tumor
    (MDPI, 2019-06-14) Mollica, Veronica; Di Nunno, Vincenzo; Gatto, Lidia; Santoni, Matteo; Scarpelli, Marina; Cimadamore, Alessia; Lopez-Beltran, Antonio; Cheng, Liang; Battelli, Nicola; Montironi, Rodolfo; Massari, Francesco; Pathology & Laboratory Medicine, IU School of Medicine
    The development of new systemic agents has led us into a "golden era" of management of metastatic renal cell carcinoma (RCC). Certainly, the approval of immune-checkpoint inhibitors and the combination of these with targeted compounds has irreversibly changed clinical scenarios. A deeper knowledge of the molecular mechanisms that correlate with tumor development and progression has made this revolution possible. In this amazing era, novel challenges are awaiting us in the clinical management of metastatic RCC. Of these, the development of reliable criteria which are able to predict tumor response to treatment or primary and acquired resistance to systemic treatments still remain an unmet clinical need. Thanks to the availability of data provided by studies evaluating genomic assessments of the disease, this goal may no longer be out of reach. In this review, we summarize current knowledge about genomic alterations related to primary and secondary resistance to target therapy and immune-checkpoint inhibitors in RCC.