Developing molecular assays to study circulating tumor DNA in a clinical setting

Our team work with the Innovation Laboratory of the Marie-Josèe and Henry R. Kravis Center for Molecular Oncology (CMO) and the Diagnostic Molecular Pathology to develop methodologies to analyze circulating tumor-derived nucleic acids (DNA/RNA) in plasma and other body fluids (such as urine and celebrospinal fluid). Our molecular assays mainly utilize massively parallel sequencing to achieve a wide range of genomic coverage and mutation detection sensitivity. Cancer types we cover include adult and pediatric solid tumors and hematological malignancies. 

In 2019, we have just completed the development and validation of a pan-cancer cfDNA profiling assay, MSK-ACCESS. It was approved by NYSDOH and launched for clinical use at MSKCC in May 2019. 

Weblink:

https://www.mskcc.org/trending-topics/msk-access-receives-new-york-stat…

Evaluating the clinical utility of circulating tumor DNA in different cancer types

Our team works with multiple early-phase clinical trial programs across MSK to study molecular profiles in longitudinal plasma and other body fluids in relation to clinical responses, with the goal of gathering information for defining clinically relevant parameters to guide treatment decisions. 

The questions we ask include:

  • How do we interpret the representations of tumor heterogeneity in plasma and other body fluids and how does it influence clinical decision?
  • How do we extract clinically relevant information from longitudinal ctDNA dynamics to monitor clinical responses?
  • We know that we can detect known resistance mechanisms in plasma before patients progress. Can we use it to discover new, unknown mechanisms?
  • Apart from circulating tumor DNA, can we study epigenetic markers (such as DNA methylation) or RNA and use the information to improve cancer management?

The cancer types we study including but not limited to: MSI-H tumors, prostate cancer, ovarian cancer, pediatric cancers, lymphoma.

Understanding the biological characteristics of circulating nucleic acid

There are many unknowns about tumor-derived circulating nucleic acids. For example, how are they transported in circulation? What is the clearance pattern? What are their physical properties in different fluids? Understanding these properties will help us tailor our strategies to utilize the information. We are particularly focusing on the cfDNA size profiles and fragmentation patterns throughout the whole genome.