RESUMO
Prostate cancer is the most common cancer among men and the second leading cause of cancer-related death. For patients who develop metastatic disease, tissue-based and circulating-tumor-based molecular and genomic biomarkers have emerged as a means of improving outcomes through the application of precision medicine. However, the benefit is limited to a minority of patients. An additional approach to further characterize the biology of advanced prostate cancer is through the use of phenotypic precision medicine, or the identification and targeting of phenotypic features of an individual patient's cancer. In this review article, we will discuss the background, potential clinical benefits, and limitations of genomic and phenotypic precision medicine in prostate cancer. We will also highlight how the emergence of image-based phenotypic medicine may lead to greater characterization of advanced prostate cancer disease burden and more individualized treatment approaches in patients.
Assuntos
Neoplasias de Próstata Resistentes à Castração , Neoplasias da Próstata , Masculino , Humanos , Medicina de Precisão , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Biomarcadores Tumorais/genética , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
Although prostate cancer is the type of cancer most commonly survived by men in the United States, it remains the second most common cause of death from cancer, largely owing to metastatic disease. Patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease has progressed on standard-of-care therapies have few options and a poor prognosis. Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein that is commonly expressed in prostate cancer. Expression is limited on extra-prostatic tissues other than the salivary glands, lacrimal glands, duodenal epithelium, Kupffer cells, and renal tubules. PSMA-directed theranostics has emerged to exploit the specificity of PSMA for prostate cancer cells and has demonstrated promising results in the clinic. Radionuclides linked to PSMA inhibitors/binders have resulted in US Food and Drug Administration (FDA) approval of 2 radiodiagnostics for PSMA-directed positron emission tomography/computed tomography. In addition, these radionuclides have led to the development of lutetium Lu 177PSMA-617 therapy, which is currently under priority FDA review. Multiple novel PSMA-targeted modalities have been developed and are currently under clinical investigation, including ligand-drug and cellular immune therapies. In this review, we discuss the development of PSMA-directed theranostics, along with its clinical implications, limitations, and future directions.
Assuntos
Próstata , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Medicina de Precisão , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Radioisótopos , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
Liquid biopsy is a promising clinical tool that can provide critical information for prognostication and which may inform treatment decisions in men with metastatic castration-resistant prostate cancer. Here we discuss the Foundation Medicine plasma cell-free circulating tumor DNA assay, its pros and cons, and potential clinical utility.See related article by Tukachinsky et al., p. 3094.
Assuntos
DNA Tumoral Circulante , Neoplasias da Próstata , Humanos , Biópsia Líquida , MasculinoRESUMO
PURPOSE: Glaucoma drainage device (GDD) implantation can lead to corneal decompensation. We evaluated changes over time in oxygen tension and in the metabolic environment of the aqueous humor after GDD implantation in the rabbit eye. METHODS: Ahmed Glaucoma Valves were implanted in the left eyes of eight male New Zealand white rabbits. Right eyes were used as a control. Oxygen tension was measured immediately before surgery and at 1 and 2 months postoperation. Aqueous humor was collected from the surgical and control eyes at 1, 2, and 5 months postoperation. Aqueous humor samples collected at 1 and 5 months postoperation were selected for broad-spectrum metabolomics analysis using ultra-performance liquid chromatography-time of flight-mass spectrometry (UPLC TOF-MS). Multivariate analysis methods were used to identify metabolite profiles that separated the surgical and control eye at 1 and 5 months. RESULTS: There was a significant decrease in oxygen tension in aqueous humor of the surgical eyes (9 mm Hg, 95% confidence interval [CI]: -14.7 to -3.5). Differences in the metabolic profiles between the surgical and control eye at 1 and 5 months were observed, as were differences for the surgical eye at 1 and 5 months. In addition, a metabolite profile was identified that differentiated the surgical eyes at 1 and 5 months. CONCLUSION: Changes in the oxygen tension and metabolic intermediates occur within the aqueous humor as early as 1 month after GDD implantation. TRANSLATIONAL RELEVANCE: Corneal decompensation following GDD implantation could be secondary to disruption of the normal aqueous circulation, resulting in hypoxia and an altered metabolic profile. Alterations to the GDD design might minimize aqueous disruption and prevent corneal decompensation.
RESUMO
PURPOSE: Up to 80% of patients with Parkinson disease and 30% of patients with amyotrophic lateral sclerosis (ALS) suffer from sialorrhea. Patients who fail medical and surgical therapy should be considered for external beam radiation therapy (EBRT). In this study, we conduct a systematic review to determine the dose and techniques used that result in greatest efficacy and lowest toxicity for the administration of EBRT in patients with Parkinson disease or ALS-associated sialorrhea. METHODS AND MATERIALS: This review included 216 patients from four prospective and six retrospective studies published from 1998 to 2014, with ALS or Parkinson disease who were treated with electron or photon EBRT for sialorrhea. RESULTS: A total of 216 patients were treated with EBRT from 10 studies. The indication for EBRT was failure of alternative medical treatment in all ALS patients. For patients with Parkinson disease, EBRT was the primary mode of treatment in 68% of cases. Overall, 176 (81%) of 216 patients treated with EBRT for sialorrhea reported symptomatic improvement from baseline. The most common target was the inferior two-thirds of the bilateral parotid glands and the entire bilateral submandibular glands. The total number of patients who experienced short-term toxicity was 86 of 216 patients (40%). The total number of patients who experienced long-term toxicity was 24 of 207 (12%). CONCLUSIONS: EBRT is an effective treatment for sialorrhea in patients suffering from ALS or Parkinson disease. Treatment to the bilateral submandibular glands and caudal parotid glands is the most common field arrangement.