Priscila Hermont Goncalves

Metabolomics in cancer: A bench-to-bedside intersection

The field of oncology is a rapidly evolving science mostly due to extensive basic, translational and clinical research which have provided more insights into the tumor biology and set grounds for the development of new therapies. Metabolomics is the upcoming new science in the omics field with the potential to further increment our knowledge of cancer biology. In this review we intend to explore the potential role of metabolomics in understanding cancer process, improving cancer staging, refining tumor characterization and in the search for predictive biomarkers of response and toxicity.

Risk of brain metastases in patients with nonmetastatic lung cancer: Analysis of the Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) data

Brain metastases (BM) remain an important cause of morbidity and mortality in patients with lung cancer. The current study evaluated population‐based incidence and outcomes of BM in patients with nonmetastatic lung cancer.

A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma

Purpose Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. Methods: Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. Results Thirty patients were enrolled. Median age of patients was 53 years (range 21–73). Median number of cycles was 5 (range 1-66). Lymphopenia (n = 5), hypertension (n = 3), oral pain (n = 2), thromboembolic events (n = 2) and fatigue (n = 2) were the only grade 3 adverse events (AEs) that occurred in more than 1 patient. Eleven patients were dose reduced secondary to drug-related AEs. Two patients had a partial response (PR), with response durations of 53 and 7.2 months. One patient had a minor response with a decrease in ascites (for 19 cycles). Stable disease was the best response in 27 patients. Targeted and WES of 8 patients in this trial identified mutations in chromatin remodeling genes highlighting the role of the epigenome in ACC. Conclusion: Vorinostat demonstrated efficacy in patients with ACC supporting the inclusion of HDACi in future studies to treat ACC.

Pulmonary Metastasis of Basal Cell Carcinoma: A Rare Manifestation of a Common Disease with Variable Clinical Course

CASE 1 A 67-year-old man presented to the Thoracic Oncology Clinic for evaluation of multiple pulmonary nodules and masses (Figure 1). The patient had a history of basal cell carcinoma involving the face that was diagnosed 18 years earlier. The tumor had multiple local recurrences that required excisions, radiation treatment, and enucleation of the left eye. He had no evidence of recurrence for 5 years before this presentation. The patient underwent computed tomography-guided biopsy of one of the pulmonary lesions. The pathology was consistent with metastatic basal cell carcinoma. Positron emission tomographic scan showed increased uptake in the pulmonary lesions with a maximum standard uptake value of 4.2. There was no abnormal activity outside the lungs. The patient had no significant pulmonary symptoms, and so he was observed with no active treatment. After 4 years of follow-up, the patient remained minimally symptomatic with no significant change in the size of the pulmonary lesions.

Abstract 5589: Molecular diagnostic, prognostic and therapeutic role of mir-221 in pancreatic cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Comprehensive molecular profiling of microRNAs (miRNAs) and subsequent target gene analysis of pancreatic cancer (PaCa) can provide tumor specific miRNAs signatures to improve diagnostic accuracy, refine prognostic and predictive capabilities, and may also serve as therapeutic targets. In PaCa such a comprehensive analysis has not been reported.Design: RNA extracted from scant amounts of formalin fixed paraffin embedded PaCa tumor and normal pancreatic tissues were profiled for miRNA expression using microfluidic biochip microarrays (which interrogate 2019 unique mature miRNAs,LC Sciences). The expression of abnormal miRNAs was then validated and quantified using real time RT-PCR. Data was statistically analyzed using the Students t-test. Survival data obtained in each case was correlated with the miRNA data using Kaplan-Meier analysis. Oncogenic potential, therapeutic modulation and downstream target genes of altered miRNA were evaluated by real time RT-PCR using PaCa cells for mRNA expression.Results: miRNA profiling showed high expression of miR-221 in PaCa tissues compared to normal pancreas (p=0.001). These findings were validated and quantified using qRT- PCR (p=0.0029) . Survival analysis using Kaplan-Meier, demonstrated shorter survival of patients with higher expression of miR-221 compared to those with relatively lower levels of miR-221 . The cell proliferation index of PaCa cells was increased by miR-221 mimics transfection and decreased by miR-221 inhibitors. The predicted target genes of miR-221 identified by RT-PCR were PTEN, p27kip1, p57kip2 and PUMA.Conclusions: High throughput miRNA expression profiling showed high expression of miR-221 in PaCa tissues. Higher levels of miR-221 demonstrated poorer prognosis, suggesting the oncogenic potential of miR-221 in PaCa. Its target genes are PTEN, p27kip1, p57kip2 and PUMA which are tumor suppressors, and found to be deregulated by over-expression or under-expression of miR-221 transfection studies in PaCa cells. These results provide molecular evidence of oncogenic potential of miR-221 in PaCa which may have a significant clinical impact on prognosis & risk stratification and in designing novel targeted molecular therapeutics in the future to achieve the goal of personalized and precision medicine. Citation Format: Seema Sethi, Shaan Sarkar, Hala Dubaybo, Shadan Ali, Priscila Goncalves, Spilakshmi Kollepara, Philip Philip, Yiwei Li. Molecular diagnostic, prognostic and therapeutic role of mir-221 in pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5589. doi:10.1158/1538-7445.AM2014-5589