Loading...
9 results
Search Results
Now showing 1 - 9 of 9
- Castration-resistant prostate cancer: mechanisms, targets, and treatmentPublication . Amaral, Teresa; Macedo, Daniela; Fernandes, Isabel; Costa, LuisPatients with castration-resistant prostate cancer (CRPC), who progress after docetaxel therapy, had until very recently, only a few therapeutic options. Recent advances in this field brought about new perspectives in the treatment of this disease. Molecular, basic, and translational research has given us a better understanding on the mechanisms of CRPC. This great investment has turned into a more rational approach to the development of new drugs. Some of the new treatments are already available to our patients outside clinical trials and may include inhibitors of androgen biosynthesis; new chemotherapy agents; bone-targeted therapy; and immunotherapy. This paper aims to review the mechanisms of prostate cancer resistance, possible therapeutic targets, as well as new options to treat CRPC.
- Osteosarcoma pathogenesis leads the way to new target treatmentsPublication . Fernandes, Isabel; Alvim, Cecilia; Brás, Raquel; Esperança Martins, Miguel; Costa, LuisOsteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.
- c-Met expression in renal cell carcinoma with bone metastasesPublication . Silva Paiva, Rita; Fernandes Gomes, Inês; Casimiro, Sandra; Fernandes, Isabel; Costa, LuisHepatocyte growth factor (HGF)/c-Met pathway is implicated in embryogenesis and organ development and differentiation. Germline or somatic mutations, chromosomal rearrangements, gene amplification, and transcriptional upregulation in MET or alterations in autocrine or paracrine c-Met signalling have been associated with cancer cell proliferation and survival, including in renal cell carcinoma (RCC), and associated with disease progression. HGF/c-Met pathway has been shown to be particularly relevant in tumors with bone metastases (BMs). However, the efficacy of targeting c-Met in bone metastatic disease, including in RCC, has not been proven. Therefore, further investigation is required focusing the particular role of HGF/c-Met pathway in bone microenvironment (BME) and how to effectively target this pathway in the context of bone metastatic disease.
- A case of success: complete response to Radium-223 in metastatic castration-resistant prostate cancerPublication . Soares De Pinho, Inês; Esperança Martins, Miguel; Machado, Bárbara; Dâmaso, Sara; Brás, Raquel; Cantinho, Guilhermina; Fernandes, Isabel; Costa, LuisRadium-223 dichloride (Ra223) is the first targeted alpha agent approved for treating metastatic castration-resistant prostate cancer (mCRPC) with bone-exclusive disease. A benefit in overall survival and time to the first symptomatic skeletal-related event was shown in the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. However, this trial did not describe a bone scan response to Ra223, and there is no universal consensus about how it should be monitored. Furthermore, a scintigraphy flare phenomenon may lead to false-positive tracer uptake in responsive cases, thereby misleading the interpretation of imaging results. We present the case of a 67-year-old male with mCRPC and exclusive bone disease treated with Ra223. The bone scintigraphy after the end of the treatment showed an apparent aggravation of the lesions, corresponding to a flare phenomenon, with an almost complete resolution after three months. The patient maintained a scintigraphic response for seven months.
- Genomic profiling of sarcomas: a promising weapon in the therapeutic arsenalPublication . Brás, Raquel; Lopez-Presa, Dolores; Esperança Martins, Miguel; Alvim, Cecilia; Gallego Páez, Lina Marcela; Costa, Luis; Fernandes, IsabelSarcomas are rare malignant mesenchymal neoplasms, and the knowledge of tumor biology and genomics is scarce. Chemotherapy is the standard of care in advanced disease, with poor outcomes. Identifying actionable genomic alterations may offer effective salvage therapeutic options when previous lines have failed. Here, we report a retrospective cohort study of sarcoma patients followed at our center and submitted to comprehensive genomic profiling between January 2020 and June 2021. Thirty patients were included, most (96.7%) with reportable genomic alterations. The most common alterations were linked to cell cycle regulation (TP53, CDKN2A/B, and RB1 deletions and CDK4, MDM2, and MYC amplifications). Most patients (96.7%) had microsatellite stability and low tumor mutational burden (≤10 muts/megabase (Mb); median 2 Muts/Mb). Two-thirds of patients had actionable mutations for targeted treatments, including five cases with alterations amenable to targeted therapies with clinical benefit within the patient's tumor type, ten cases with targetable alterations with clinical benefit in other tumor types, and five cases with alterations amenable to targeting with drugs under investigation in a clinical trial setting. A significant proportion of cases in this study had actionable genomic alterations with available targeted drugs. Next-generation sequencing is a feasible option for identifying molecular drivers that can provide therapeutic options for individual patients. Molecular Tumor Boards should be implemented in the clinical practice to discuss genomic findings and inform clinically relevant targeted therapies.
- A tailored approach for appendicular impending and pathologic fractures in solid cancer metastasesPublication . Soares Do Brito, Joaquim; Brás, Raquel; Abrunhosa-Branquinho, André; Fernandes, Isabel; Fernandes Gomes, Inês; Casimiro, Sandra; Costa, LuisAdvances in medical and surgical treatment have played a major role in increasing the survival rates of cancer patients with metastatic bone disease. The clinical course of patients with bone metastases is often impaired by bone complications, such as bone fractures, which have a substantial negative impact on clinical outcomes. To optimize clinical results and prevent a detrimental impact on patients' health, a tailored approach should be defined for any given patient. The optimal management of impending or pathologic fractures is unknown and relies on a multidisciplinary approach to tailor clinical decisions to each individual patient. The ability to control systemic disease, the extent, location and nature of bone metastases, and the biology of the underlying tumor, are the main factors that will define the strategy to follow. The present review covers the most recent data regarding impending and pathologic fractures in patients with bone metastases, and discusses the medical and surgical management of patients presenting with metastatic bone disease in different clinical settings.
- Prognostic factors for patients treated with abirateronePublication . Alvim, Cecilia; Mansinho, André; Paiva, Rita S.; Brás, Raquel; Semedo, Patrícia M.; Lobo-Martins, Soraia; da Ponte, Carolina B.; Macedo, Daniela; Ribeiro, Maria Leonor; dos Reis, José P; Fernandes, Isabel; Costa, LuisAim: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Methods: Retrospective evaluation of patients with mCRPC treated with AA. Results: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10-0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14-0.41; p < 0.001). Conclusion: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.
- The treatment of liver metastases in patients with neuroendocrine tumors in 2012Publication . Macedo, Daniela; Amaral, Teresa; Fernandes, Isabel; Sousa, Ana Rita; Costa, Ana Lúcia; Távora, Isabel; Quintela, António; Cortes, Paulo; Costa, LuisNeuroendocrine tumors (NETs) comprise a heterogeneous group of tumors that form a distinct entity. Approximately 75-80% of patients present with liver metastases at the time of their diagnosis, and 20%-25% will develop these lesions in the course of their disease. The presence of secondary deposits in the liver significantly increases the morbidity and mortality in these patients. The only potentially curative treatment is the surgical resection of the primary tumor and hepatic lesions. However, only 10% of patients presents under ideal conditions for that approach. Several techniques aimed at localized liver lesions have been applied also with interesting results in terms of survival and symptom control. The same has been demonstrated with new systemic therapies (target therapies). However, these are still under study, in order to define their true role in the management of these patients. This paper intends to address, in a general way, the various treatment options in patients with liver metastases from neuroendocrine tumors.
- Prognostic significance of AKT/mTOR signaling in advanced neuroendocrine tumors treated with somatostatin analogsPublication . Fernandes, Isabel; Pacheco, Teresa; Costa, Adília; Santos, Ana C.; Fernandes, Ana R.; Santos, Mara; Oliveira, António G.; Casimiro, Sandra; Quintela, António; Fernandes, Afonso; Ramos, Madalena; Costa, LuisIntroduction: Somatostatin analogs (SSAs) are used as part of standard treatment for advanced neuroendocrine tumors (NETs). The mechanisms behind the antiproliferative action of SSAs remain largely unknown, but a connection with the mammalian target of rapamycin (mTOR) signaling pathway has been suggested. Our purpose was to evaluate the activation status of the AKT/mTOR pathway in advanced metastatic NETs and identify biomarkers of response to SSA therapy. Patients and methods: Expression of phosphatase and tensin homolog (PTEN), phosphorylated (p)-AKT(Ser473), and p-S6(Ser240/244) was evaluated using immunohistochemistry in archival paraffin samples from 23 patients. Expression levels were correlated with clinicopathological parameters and progression-free survival under treatment with SSAs. Results: A positive association between p-AKT and p-S6 expression was identified (P = 0.01) and higher expression of both markers was observed in pancreatic NETs. AKT/mTOR activation was observed without the loss of PTEN expression. Tumors showing AKT/mTOR signaling activation progressed faster when treated with SSAs: higher expression of p-AKT or p-S6 predicted a median progression-free survival of 1 month vs 26.5 months for lower expression (P = 0.02). Conclusion: Constitutive activation of the AKT/mTOR pathway was associated with shorter time-to-progression in patients undergoing treatment with SSAs. Larger case series are needed to validate whether p-AKT(Ser473) and p-S6(Ser240/244) can be used as prognostic markers of response to therapy with SSAs.