Biomarker Of Response In Patients Research Articles

Abstract PL03-01: Discovery of candidate biomarkers of anticancer drug sensitivity by high-throughput cell line screening.

Abstract PL03-01: Discovery of candidate biomarkers of anticancer drug sensitivity by high-throughput cell line screening.

Functional magnetic resonance: biomarkers of response in breast cancer

Functional magnetic resonance (MR) encompasses a spectrum of techniques that depict physiological and molecular processes before morphological changes are visible on conventional imaging. As understanding of the pathophysiological and biomolecular processes involved in breast malignancies evolves, newer functional MR techniques can be employed that define early predictive and surrogate biomarkers for monitoring response to chemotherapy. Neoadjuvant chemotherapy is increasingly used in women with primary breast malignancies to down-stage the tumour and enable successful breast conservation surgery. It also plays a role in the treatment of undetected micrometastases. Cardinal physiological features of tumours that occur as a result of interactions between cancer cells, stromal cells and secreted factors and cytokines and how they change with treatment provide the opportunity to detect changes in the tumour microenvironment prior to any morphological change. Through sequential imaging, tumour response can be assessed and non-responders can be identified early to enable alternative therapies to be considered. This review summarises the functional magnetic resonance biomarkers of response in patients with breast cancer that are currently available and under development. We describe the current state of each biomarker and explore their potential clinical uses and limitations in assessing treatment response. With the aid of selected interesting cases, biomarkers related to dynamic contrast-enhanced MRI, diffusion-weighted MRI, T2*/BOLD and MR spectroscopy are described and illustrated. The potential of newer approaches, such as MR elastography, are also reviewed.

A randomized phase II trial of chemoradiotherapy with oral fluoropyrimidine inhibitory for dihydropyrimidine dehydrogenase for low rectal cancer: An interim report.

524 Background: Preoperative chemoradiotherapy (CRT) has been widely used to improve local control of disease and to preserve anal sphincter in the treatment of rectal cancer. However, the response to CRT differs among individual tumors. In ASCO 2008 Gastrointestinal Cancers Symposium, we reported that the patients with up-regulation of 17 genes were suggested to be good responder of CRT. Our purpose of this study was to evaluate the toxicity and efficacy of CRT using UFT versus S-1 and explore biomarkers for response in patients with locally advanced rectal cancer. Methods: Fifty patients who received preoperative CRT (40Gy radiotherapy) were randomly assigned to either UFT or S-1. UFT and S-1 were administered during the radiotherapy course. S-1 was a novel oral fluoropyrimidine inhibitory for dihydropyrimidine dehydrogenase and had potent radiosensitizing property. Biopsy specimens were obtained from rectal cancer before preoperative CRT and were analyzed by focused DNA microarray (132 genes). To pick up the predictive factors, the 132 genes were selected in the view of sensitivity of 5FU. Response to CRT was determined by RECIST and histopathologic examination of surgically resected specimens and classified as responders (CR, PR and grade 2, 3) or nonresponders (SD, PD and grade 0, 1). Results: UFT group (n=25) and S-1 group (n=25) were enrolled. Response rate (grade 2 or 3) to CRT determined by histopathologic examination of surgically resected specimens was 58% in the UFT group and was 75% in the S-1 group. Response rate evaluated by RECIST criteria was 62% in the UFT group and was 77% in the S-1 group. National Cancer Institute Common Toxicity Criteria grade 2 or 3 toxicity was observed in 8% of the patients in the UFT group and 23% of patients in the S-1 group. Grade 2 or 3 toxicity in the UFT group was neutropenia and was diarrhea, neutropenia and dermatitis in the S-1 group. In ASCO 2010, we will report each candidate biomarker genes for response to CRT in the UFT and S-1 group. Conclusions: The results have suggested that CRT using UFT or S-1 is feasible and effective for patients with locally advanced rectal cancer. [Table: see text]

Abstract 4673: Myopodin methylation is a prognostic marker in patients with T1G3 bladder cancer

Abstract BACKGROUND: Urothelial carcinomas presenting T1G3 non muscle-invasive lesions are high-risk tumors because of the high recurrence and progression to muscle invasive disease rates. The Bacillus of Calmette-Guérin (BCG) is a standard treatment to reduce tumor recurrence and delay progression of high-risk non-muscle invasive bladder tumors. However, it is not clear yet which T1G3 patients are more prone to display a more aggressive clinical behavior or be susceptible to respond to BCG. OBJECTIVE: The aim of this study was to evaluate the role of myopodin methylation as a clinical outcome prognosticator and predictive biomarker for BCG response in patients with T1G3 bladder tumors. DESIGN, SETTING, AND PARTICIPANTS: The methylation status of myopodin was analyzed on tumor specimens belonging to 170 patients with T1G3 non-muscle invasive bladder cancer, being a subset of them undergoing BCG treatment (n=108). MEASUREMENTS: Myopodin methylation was assessed by methylation-specific polymerase chain reactions. Recurrence, progression into muscle invasive tumors and disease-specific overall survival rates were analyzed using competing risks regression analysis. RESULTS: Among the 170 cases analyzed, 72 of them recurred (42.4%), 36 progressed (21.2%), and 24 died of the disease (14.1%). Univariate and multivariate survival analyses revealed that myopodin methylation was significantly associated with an increased recurrence rate (p=0.004), progression (p=0.002), and shorter disease-specific overall survival (p=0.020). Interestingly, in a subset of cases treated with BCG, myopodin methylation was also related to an increased recurrence rate (p=0.011), progression (p=0.030), and a shorter disease-specific overall survival (p=0.028). CONCLUSIONS: Epigenetic analyses revealed that myopodin methylation was associated with the clinical outcome of patients with T1G3 tumors. Myopodin methylation was related to tumor aggressiveness in patients with T1G3 disease undergoing BCG treatment. Myopodin methylation distinguished patients responding to BCG from those who may require a more aggressive therapeutic approach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4673.