Mission Bio Inc, South San Francisco, Calif, a pioneer in high-throughput single-cell DNA analysis and precision genomics, has published a study demonstrating the power of its Tapestri platform to help predict and prevent cancer progression.1
The study is the first to use single-cell DNA analysis to reveal how cancer evolves in response to targeted treatment, leading to therapy resistance and disease progression in patients with acute myeloid leukemia (AML). Although new targeted therapies have been approved to treat AML, drug resistance and disease progression remain a challenge. Single-cell resolution empowers researchers to describe the polyclonality that underlies clinical resistance to targeted agents and, in turn, to take steps to better suppress resistance.
FDA recently approved the cancer drug gilteritinib, an FLT3 inhibitor, for treating relapsed or refractory AML. However, the polyclonality of AML makes therapy resistance a prominent hurdle, as cell populations or clones evolve and acquire mutations that evade the targeted therapy. Current methods in cancer diagnosis and care include bulk next-generation sequencing (NGS), which relies on sample averages and therefore misses the underlying genetic diversity driving the disease and affecting treatment response. To create effective, dynamic therapies, it is essential that researchers have a deep understanding of each tumor’s true heterogeneity and precise resistance mechanisms.
The study was led by researchers from the University of Pennsylvania and the University of California, San Francisco. The researchers sought to characterize the clonal evolution of AML at the single-cell level, identifying multiple resistance clones missed by traditional sequencing methods.
Leveraging Mission Bio’s high-throughput single-cell targeted DNA sequencing technology, the Tapestri platform, the lab analyzed retrospective longitudinal sample sets from patients treated in clinical trials. The researchers were able to monitor the clonal progression of AML in response to targeted therapy with gilteritinib, ultimately revealing preexisting and treatment-emergent clones that activated the RAS/MAPK signaling pathway, thus driving subsequent therapy resistance.
The study insights illuminate not just the need for high-resolution monitoring of patient response to targeted treatment, but also uncover the potential to develop more impactful, dynamic therapies for those with advanced AML.
“Cancer is a dynamic—even ‘smart’—disease, constantly evolving to evade treatment,” explains cosenior author Catherine Smith, MD, an assistant professor of medicine at UCSF. “In monitoring how the disease evolves and develops clinical resistance, we have the potential to apply dynamic therapies that mirror the dynamics of the disease. These findings put us on the precipice of the next frontier of precision medicine.”
“Empowering breakthroughs that can save patient lives is key to our work at Mission Bio,” says Charlie Silver, cofounder and CEO. “Our Tapestri platform is uniquely equipped to translate these meaningful discoveries in single-cell genomics to the clinic and make a real difference in patient care and outcomes.”
Tapestri is the first single-cell DNA sequencing platform, enabling precise detection of heterogeneity in disease progression and treatment response. Application areas include blood cancers, solid tumors, and genome editing validation. The platform includes an instrument, consumables, and software that plug seamlessly into existing NGS workflows.
For further information, visit Mission Bio.
1. McMahon CM, Ferng T, Canaani J, et al. Clonal selection with RAS pathway activation mediates secondary clinical resistance to selective FLT3 inhibition in acute myeloid leukemia. Cancer Discov. Epub before print, May 14, 2019; doi: 10.1158/2159-8290.cd-18-1453.