Powerful Prognostic Tools
Dave Hoon, Ph.D., director of molecular oncology at the John Wayne Cancer Institute, will also speak at the “Molecular Medicine TriConference”. He will present the results of two Phase III multicenter randomized clinical trials that demonstrate that circulating tumor cells (CTCs) are an independent prognostic factor for disease-free and overall survival in patients with stage 3 and 4 melanoma. Dr. Hoon and colleagues developed a multimarker real-time quantitative reverse transcriptase assay designed to detect and quantify CTCs in the blood of patients with melanoma.
The RT-qPCR assay measures the levels of four melanoma-associated CTC mRNAs: MART-1, GalNAc-T, PAX3, and MAGE-A3. In Phase II trials, the presence of and increasing numbers of these biomarkers, measured serially in patients undergoing combination immunotherapy and chemotherapy, correlated with disease progression, treatment response, and overall and disease-free survival.
“This is a direct blood assay” performed on mRNA isolated from whole cells in patients’ blood samples, says Dr. Hoon. Its advantages include being real-time, probe-based, highly specific, and optimized for the biomarkers selected. The rationale behind designing a multimarker assay was based on the heterogeneity of tumors and CTCs, making it unlikely that a single marker would be predictive, particularly in aggressive disease with different sites of origin.
“Tumor cells that express these markers are more aggressive. It is not the number of CTCs that is prognostic; rather it is the content of the cells,” Dr. Hoon says. The goal is to develop this assay as a blood test for use in predicting which treatment is likely to be most effective following surgery, for determining disease spread, and for monitoring the effectiveness of adjuvant therapy.