This past February, four grant program applicants were awarded nCounter Vantage 3D™ Assays of their choice to profile 36 samples. NanoString followed up with each of the winners to explore how they intend to use the assays to advance their research.
Grant Winner: Holly Yin, Ph.D., City of Hope National Medical Center
Grant Abstract Title: Identification and verification of druggable target(s) in cutaneous melanoma without BRAF or RAS mutations
“People can do RNA, but for protein we are doing ELISA or Western Blot, one at a time. Or IHC, which is also only one at a time. Adding protein in a more multiplex style is definitely adding value. The best is you can do all three [analytes] in one shot. I’m really hoping this will help me to identify the target for BRAF wild-type patients in melanoma.” – Dr. Yin
Project Summary: This project aims to identify and verify novel genes and pathways involved in the survival of melanoma cells without BRAF and RAS mutations. Importantly, a significant proportion of tumors harbor neither the BRAF nor RAS mutations typically associated with constitutive MAPK pathway signaling (estimated to be 30-40% of melanomas), and thus the development of novel targeted approaches for treatment is a critical need. The expectation is to identify genes and pathways that have drastic changes at the DNA, RNA, or protein levels (with significant p-values) between the wild-type and mutant groups. With a large collection of melanoma FFPE samples with molecular characterization of BRAF and RAS mutation status (100 samples in total), all treatment-naïve samples will be curated and paired with 6 samples of wild-type BRAF and RAS versus BRAF V600E mutants.
Grant Winner: Hélène Blons, Ph.D., Head of the Pharmacogenetics and Molecular Oncology Unit, Georges Pompidou European Hospital, INSERM
Grant Abstract Title: Identification and prognostic impact of a metastases facilitator pattern in resected non-small cell lung cancer IIIA-N2
“We don’t always have frozen tissue for the patients and we don’t always have a large amount of tissue available to do whatever we want to do for those patients. The use of techniques that are compatible with small samples is beneficial, as low DNA quantity and sometimes low DNA quality is the major challenge that we have to deal with.” – Dr. Blons
Project Summary: The hypothesis is that tumor heterogeneity is related to higher adaptation capacities (in nodes, in blood stream, and eventually in bone marrow) and to cell plasticity leading to potential resistance to treatment and ultimately to worse prognosis. IIIA-N2 NSCLC is a good model to study tumor heterogeneity with multiple samples available after surgery. Comprehensive analysis of match pairs (primitive tumors and N2 node) will help analyze differences between long term survivors and early relapse patients to identify those who will benefit from surgery. Using 3D Biology™ technology for research purposes, there is an opportunity to test pathways to see if there is a signature at the expression level that helps identify the good responders to the surgery versus the ones that will relapse early. In this project, the goal is to define a specific metastases facilitator pattern associated to prognosis in resected IIIA-N2 NSCLC. Oncogene/tumor suppressor genetic profiles and expression data will be evaluated to link genotypes to pathway activation in the primary tumor as well as in N2 nodes to identify the good responders to the surgery versus the one that will relapse early.
Grant Winner: Chanthirika Ragulan, The Institute of Cancer Research, United Kingdom
Grant Abstract Title: Can the nCounter Vantage 3D assay stratify pancreatic adenocarcinoma patients who may benefit from FOLFIRINOX chemotherapy treatment?
“In pancreatic cancer obtaining adequate samples for translational work has historically been difficult, hampering progress, but being able to compare genotype, gene, and protein expression in a single view will enable us to make the most of these FFPE samples.” – C. Ragulan
Project Summary: There is now an urgent need to capitalize on advances in subtyping, to consider rational novel therapeutic combinations, and to develop methods to appropriately select those who may benefit. The assays provide an opportunity to fully interrogate these precious samples and obtain the maximum biological data possible. With a clinical database of over 100 patients who have been treated with chemotherapy at the Royal Marsden Hospital 36 patients with poor or exceptional responses to chemotherapy will be selected. Using 3D Biology Technology, the molecular or immune basis for the disparity in treatment response will be assessed. This pilot study will form a basis for further research in PDAC, considering the role of subtyping in predicting response to other treatments, including immunotherapy, and will enable to plan future translational clinical studies with optimum patient selection to maximize the chance of successful treatment for patients.
Grant Winner: Doaa Tawfik, M.D., Institute of Experimental Cancer Research, Christian-Albrechts University, Germany
Grant Abstract Title: Molecular mechanisms behind the intracellular functions of the TRAIL receptors in PDAC cell lines
“Our studies will aid in understanding the role of TRAIL receptors in cancer and eventually lead to the development of novel therapeutic strategies for PDAC patients.” – Dr. Tawfik
Project Summary: Pancreatic ductal adenocarcinoma (PDAC) is a notorious cancer known for its difficult diagnosis, resistance to treatment, and an overall bad prognosis. A deeper understanding of its development and progression is urgently needed. By analyzing molecular changes at the DNA, RNA, and protein levels in parallel, the key molecular players involved in TRAIL receptor-mediated actions in PDAC can be identified. The goal of this project is to start defining the molecular differences (on the DNA mutation level, RNA, and protein levels) between the various PDAC cell lines to understand the mechanism(s) and the possible pathways driven by the TRAIL receptors in the pathogenesis of PDAC. Additionally, it will aid in understanding the role of these receptors in cancer and eventually lead to the development of novel therapeutic strategies for PDAC patients.
The nCounter® Vantage 3D™ Assays enable simultaneous quantification of DNA, RNA, protein, and protein post-translational modifications from a single sample, defined as 3D Biology™ Technology. This approach removes potential amplification bias, uses less precious material to gather more informative data, and simplifies analysis by comparing genotype and phenotype in a single view.
Find more information on how 3D Biology Technology can make a difference in your research.
FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.