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- Comparative cost-effectiveness analysis of avelumab plus axitinib versus pembrolizumab plus axitinib, ipilimumab plus nivolumab, and sunitnib for advanced renal cell carcinoma in the UK perspectivePublication . De Mello, Ramon Andrade; Ayoub, Emili; Castelo-Branco, Pedro; De Almeida Zia, Victor Andre; Savio, Andre; Pozza, Daniel Humberto; Tadokoro, Hakaru; Teich, Nelson
- EGFR and EML4-ALK updated therapies in non-small cell lung cancer.Publication . Mello, Ramon Andrade de; Liu, Davi J J; Aguiar, Pedro N; Tadokoro, HakaruBACKGROUND: Non-small cell lung cancer is the leading cancer-related cause of death.OBJECTIVE: We review the latest therapies for NSCLC with EGFR and ELM4-ALK mutations as well as the most relevant studies and promising patents.METHOD: A literature search of PubMed database was carried out to identify recent Clinical Trials using EGFR therapies and novel patents involving diagnosis and therapies on NSCLC. We conducted a search to find new therapy strategies, new biomarkers, and selected five patents we find relevant.RESULTS: Over the last few years, identification of cancer harboring epidermal growth factor receptor mutations (EGFR) or chromosomal rearrangements of anaplastic lymphoma kinase (ALK) led to new ways in classifying and treating NSCLC. On the other hand, acquired resistance are a constantly challenge in the management of patients with these mutations and new drugs options are in development to improve and amplify treatment strategies.CONCLUSIONS: Currently, EGFR TKIs (e.g.: erlotinib, gefitinib, osimertinib) and ALK inhibitors (crizotinib, ceritinib, alectinib) provided a new face for advanced NSCLC outcomes. To understand the disease molecular profile is mandatory to define the best approach for each patient.
- CRISPR-based strategies in infectious disease diagnosis and therapyPublication . Binnie, Alexandra; Fernandes, Emanuel; Almeida‑Lousada, Helder; De Mello, Ramon Andrade; Castelo-Branco, PedroCRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called "molecular scissors" enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases.
- MicroRNAs in lung cancerPublication . Castro, Diana; Moreira, Marcia; Gouveia, Alexandra Monteiro; Pozza, Daniel Humberto; De Mello, Ramon AndradeLung cancer (LC) is a serious public health problem responsible for the majority of cancer deaths and comorbidities in developed countries. Tobacco smoking is considered the main risk factor for LC; however, only a few smokers will be affected by this cancer. Current screening methods are focused on identifying the early stages of this malignancy. Thus, new data concerning the roles of microRNA alterations in inflammation, epithelial-mesenchymal transition and lung disease have increased hope about LC pathogenesis, diagnosis, treatment and prognosis. MicroRNA mechanisms include angiogenesis promotion, cell cycle regulation by modulating cellular proliferation and apoptosis, and migration and invasion inhibition. In this context, this manuscript reviews the current information about many important microRNAs as they relate to the initiation and progression of LC.
- Cetuximab plus platinum-based chemotherapy in head and neck Squamous Cell Carcinoma: a retrospective study in a single Comprehensive European Cancer InstitutionPublication . De Mello, Ramon Andrade; Gerós, Sandra; Alves, Marcos Pantarotto; Moreira, Filipa; Avezedo, Isabel; Dinis, JoseBackground: The use of cetuximab in combination with platinum (P) plus 5-fluorouracil (F) has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN). We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS), progression-free-survival (PFS), overall response rate (ORR) and the treatment toxicity profile in a retrospective cohort. Patients and Methods: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. Results: The median patient age was 53 (37-78) years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316) and PFS of 8 months (CI 95%, 6.051-9.949). The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%), skin rash (3.8%) and mucosistis (3.8%). Conclusions: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.
- Epigenetic therapy in urologic cancers: an update on clinical trialsPublication . Faleiro, Inês; Leão, Ricardo; Binnie, Alexandra; De Mello, Ramon Andrade; Maia, Ana Teresa; Castelo-Branco, PedroEpigenetic dysregulation is one of many factors that contribute to cancer development and progression. Numerous epigenetic alterations have been identified in urologic cancers including histone modifications, DNA methylation changes, and microRNA expression. Since these changes are reversible, efforts are being made to develop epigenetic drugs that restore the normal epigenetic patterns of cells, and many clinical trials are already underway to test their clinical potential. In this review we analyze multiple clinical trials (n=51) that test the efficacy of these drugs in patients with urologic cancers. The most frequently used epigenetic drugs were histone deacetylase inhibitors followed by antisense oligonucleotides, DNA methyltransferase inhibitors and histone demethylase inhibitors, the last of which are only being tested in prostate cancer. In more than 50% of the clinical trials considered, epigenetic drugs were used as part of combination therapy, which achieved the best results. The epigenetic regulation of some cancers is still matter of research but will undoubtedly open a window to new therapeutic approaches in the era of personalized medicine. The future of therapy for urological malignancies is likely to include multidrug regimens in which epigenetic modifying drugs will play an important role.
- The TERT hypermethylated oncologic region predicts recurrence and survival in pancreatic cancerPublication . Faleiro, Inês; Apolónio, Joana; Price, Aryeh J.; De Mello, Ramon Andrade; Roberto, Vânia; Tabori, Uri; Castelo-Branco, PedroAim: We explore the biomarker potential of the TERT hypermethylated oncologic region (THOR) in pancreatic cancer. Materials & methods: We assessed the methylation status of THOR using the cancer genome atlas data on the cohort of pancreatic cancer (n = 193 patients). Results: THOR was significantly hypermethylated in pancreatic tumor tissue when compared with the normal tissue used as control (p < 0.0001). Also, THOR hypermethylation could distinguish early stage I disease from normal tissue and was associated with worse prognosis. Discussion: We found that THOR is hypermethylated in pancreatic tumor tissue when compared with normal tissue and that THOR methylation correlates with TERT expression in tumor samples. Conclusion: Our preliminary findings support the diagnostic and prognostic values of THOR in pancreatic cancer.
- A pooled analysis of nivolumab for the treatment of advanced non-small-cell lung cancer and the role of PD-L1 as a predictive biomarkerPublication . Aguiar, Pedro N., Jr.; Santoro, Ilka Lopes; Tadokoro, Hakaru; Lopes, Gilberto de Lima; Filardi, Bruno Andraus; Oliveira, Pedro; Castelo-Branco, Pedro; Mountzios, Giannis; de Mello, Ramon AndradeBackground: Recent studies with nivolumab (a monoclonal antibody against programmed cell death 1 [PD-1] receptor) have shown promise non-small-cell lung cancer (NSCLC) treatment. Methods: To review available clinical trials data in order to assess nivolumab efficacy and the role of tumoral PDL-1 expression as a biomarker. Results: Nine eligible studies included 2102 patients. In the second line setting, nivolumab achieved a 1-year survival rate of 41%; and in the first line, a 1-year survival rate of 76%. For those with PD-L1 expression <1%, nivolumab showed a trend for improved survival compared with docetaxel. Conclusions: The available data reinforce nivolumab activity against NSCLC in first-line or subsequent lines. Although PD-L1 expression is related to greater response, PD-L1 negative patients had also some benefit.
- PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival dataPublication . Aguiar, Pedro N., Jr.; De Mello, Ramon Andrade; Hall, Peter; Tadokoro, Hakaru; de Lima, GilbertoAim: The treatment of non-small-cell lung cancer has changed after the development of the immune checkpoint inhibitors. Although the most studied biomarker is the tumor programmed death ligand one (PD-L1) expression, its clinical significance is still debatable. In this article, we show the updated survival analysis of all published data. Methods: We searched in network and conference data sources for relevant clinical studies of immunotherapy for non-small-cell lung cancer that assessed the PD-L1 expression even as an exploratory analysis. The updated survival hazard ratios (HR) were included in the analysis. Results: 14 studies with 2857 patients were included (2019 treated with immunotherapy). The response rate was as higher among PD-L1-positive patients (RR: 2.19, 95% CI: 1.63-2.94). PD-L1 expression was also related to better progression-free survival (HR: 0.69, 95% CI: 0.57-0.85) and better overall survival (HR: 0.77, 95% CI: 0.67-0.89). Conclusion: PD-L1 overexpression predicts activity as well as better survival for patients treated with immune checkpoint inhibitors.
- Potential role of immunotherapy in advanced non-small-cell lung cancerPublication . De Mello, Ramon Andrade; Veloso, Ana Flavia; Catarina, Paulo Esrom; Nadine, Sara; Antoniou, GeorgiosImmuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD- 1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs. Here, we discuss advances in immunotherapy for the treatment of metastatic non-small-cell lung cancer as well as future perspectives within this framework.
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