IU Indianapolis ScholarWorks :: Browsing by Author "Massari, Francesco"

Browsing by Author "Massari, Francesco"

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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.
Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications
(MDPI, 2020-12) Aurilio, Gaetano; Cimadamore, Alessia; Mazzucchelli, Roberta; Lopez-Beltran, Antonio; Verri, Elena; Scarpelli, Marina; Massari, Francesco; Cheng, Liang; Santoni, Matteo; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
Around 80–90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient’s response to androgen ablation therapy is variable, and 20–30% of PCa cases become castration resistant (CRPCa). Several mechanisms can guide treatment resistance to anti-AR molecules. In this regard, AR-dependent and -independent resistance mechanisms can be distinguished within the AR pathway. In this article, we investigate the multitude of AR signaling aspects, encompassing the biological structure of AR, current AR-targeted therapies, mechanisms driving resistance to AR, and AR crosstalk with other pathways, in an attempt to provide a comprehensive review for the PCa research community. We also summarize the new anti-AR drugs approved in non-metastatic castration-resistant PCa, in the castration-sensitive setting, and combination therapies with other drugs.
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
Circulating Tumor Cells in Renal Cell Carcinoma: Recent Findings and Future Challenges
(Frontiers, 2019-04-05) Santoni, Matteo; Cimadamore, Alessia; Cheng, Liang; Lopez-Beltran, Antonio; Battelli, Nicola; Massari, Francesco; Scarpelli, Marina; Galosi, Andrea Benedetto; Bracarda, Sergio; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
Circulating Tumor DNA Testing for Homology Recombination Repair Genes in Prostate Cancer: From the Lab to the Clinic
(MDPI, 2021-05-24) Cimadamore, Alessia; Cheng, Liang; Massari, Francesco; Santoni, Matteo; Pepi, Laura; Franzese, Carmine; Scarpelli, Marina; Lopez-Beltran, Antonio; Benedetto Galosi, Andrea; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
Approximately 23% of metastatic castration-resistant prostate cancers (mCRPC) harbor deleterious aberrations in DNA repair genes. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) therapy has shown improvements in overall survival in patients with mCRPC who harbor somatic and/or germline alterations of homology recombination repair (HRR) genes. Peripheral blood samples are typically used for the germline mutation analysis test using the DNA extracted from peripheral blood leucocytes. Somatic alterations can be assessed by extracting DNA from a tumor tissue sample or using circulating tumor DNA (ctDNA) extracted from a plasma sample. Each of these genetic tests has its own benefits and limitations. The main advantages compared to the tissue test are that liquid biopsy is a non-invasive and easily repeatable test with the value of better representing tumor heterogeneity than primary biopsy and of capturing changes and/or resistance mutations in the genetic tumor profile during disease progression. Furthermore, ctDNA can inform about mutation status and guide treatment options in patients with mCRPC. Clinical validation and test implementation into routine clinical practice are currently very limited. In this review, we discuss the state of the art of the ctDNA test in prostate cancer compared to blood and tissue testing. We also illustrate the ctDNA testing workflow, the available techniques for ctDNA extraction, sequencing, and analysis, describing advantages and limits of each techniques.
Contemporary grading of prostate cancer: 2017 update for pathologists and clinicians
(Wolters Kluwer, 2017-08-04) Gasparrini, Silvia; Cimadamore, Alessia; Scarpelli, Marina; Massari, Francesco; Doria, Andrea; Mazzucchelli, Roberta; Cheng, Liang; Lopez-Beltran, Antonio; Montironi, Rodolfo; Pathology and Laboratory Medicine, School of Medicine
The Gleason grading system for prostate cancer (PCa) was developed in the 1960s by DF Gleason. Due to changes in PCa detection and treatment, the application of the Gleason grading system has changed considerably in pathology routine practice. Two consensus conferences were held in 2005 and in 2014 to update PCa Gleason grading. This review provides a summary of the changes in the grading of PCa from the original Gleason grading system to the prognostic grade grouping, as well as a discussion of the clinical significance of the percentage of Gleason patterns 4 and 5.
Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma
(MDPI, 2020-06-02) Mollica, Veronica; Rizzo, Alessandro; Montironi, Rodolfo; Cheng, Liang; Giunchi, Francesca; Schiavina, Riccardo; Santoni, Matteo; Fiorentino, Michelangelo; Lopez-Beltran, Antonio; Brunocilla, Eugenio; Brandi, Giovanni; Massari, Francesco; Pathology and Laboratory Medicine, School of Medicine
Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately 15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials.
Emerging Molecular Technologies in Renal Cell Carcinoma: Liquid Biopsy
(MDPI, 2019-02-07) Cimadamore, Alessia; Gasparrini, Silvia; Massari, Francesco; Santoni, Matteo; Cheng, Liang; Lopez-Beltran, Antonio; Scarpelli, Marina; Montironi, Rodolfo; Department of Pathology and Laboratory Medicine, IU School of Medicine
Liquid biopsy, based on the circulating tumor cells (CTCs) and cell-free nucleic acids has potential applications at multiple points throughout the natural course of cancer, from diagnosis to follow-up. The advantages of doing ctDNA assessment vs. tissue-based genomic profile are the minimal procedural risk, the possibility to serial testing in order to monitor disease-relapse and response to therapy over time and to reduce hospitalization costs during the entire process. However, some critical issues related to ctDNA assays should be taken into consideration. The sensitivity of ctDNA assays depends on the assessment technique and genetic platforms used, on tumor-organ, stage, tumor heterogeneity, tumor clonality. The specificity is usually very high, whereas the concordance with tumor-based biopsy is generally low. In patients with renal cell carcinoma (RCC), qualitative analyses of ctDNA have been performed with interesting results regarding selective pressure from therapy, therapeutic resistance, exceptional treatment response to everolimus and mutations associated with aggressive behavior. Quantitative analyses showed variations of ccfDNA levels at different tumor stage. Compared to CTC assay, ctDNA is more stable than cells and easier to isolate. Splice variants, information at single-cell level and functional assays along with proteomics, transcriptomics and metabolomics studies can be performed only in CTCs.
Evaluation of an institutional series of low-grade oncocytic tumor (LOT) of the kidney and review of the mutational landscape of LOT
(Springer, 2023) Ricci, Costantino; Ambrosi, Francesca; Franceschini, Tania; Giunchi, Francesca; Grillini, Alessia; Franchini, Eugenia; Grillini, Marco; Schiavina, Riccardo; Massari, Francesco; Mollica, Veronica; Tateo, Valentina; Bianchi, Federico Mineo; Bianchi, Lorenzo; Droghetti, Matteo; Maloberti, Thais; Tallini, Giovanni; Colecchia, Maurizio; Acosta, Andres Martin; Lobo, João; Trpkov, Kiril; Fiorentino, Michelangelo; de Biase, Dario; Pathology and Laboratory Medicine, School of Medicine
The 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of LOT, by selecting papers in which LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43–79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9–3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without “canonical” mutations.
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.

Browsing by Author "Massari, Francesco"

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