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Human Tumor Atlas Network Team Shares Strategy for Tracking Tumor Transitions

NEW YORK – A team from the Broad Institute, the Massachusetts Institute of Technology, Memorial Sloan Kettering Cancer Center, and elsewhere has outlined progress made so far on the Human Tumor Atlas Network (HTAN), an effort to follow cancer development, progression, and treatment response over time using a series of single-cell atlases.

"This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time," corresponding and co-first author Aviv Regev, an integrative cancer researcher affiliated with the Broad and MIT, and his co-authors wrote in a paper published in Cell on Thursday.

Through the National Cancer Institute's Cancer Moonshot Initiative, Regev and his colleagues plan to conduct single-cell RNA sequencing or single-nucleus RNA-seq — combined with spatial information, exome sequences, proteomic profiles, epigenomic data, metabolomic and microbiome clues, and more — to look at mutations, copy number changes, expression shifts, and other alterations in 3D in pre-cancerous, malignant, and metastatic cancer samples from several adult and pediatric cancer types.

In the new paper, the team set out the rationale for this effort, details on the analyses and methods proposed, and insights into the tissue and tumor types that will be assessed at centers across 10 interdisciplinary cancer centers in the US over the next five years. While centers such as the Children's Hospital of Philadelphia plan to focus on primary and treatment-resistant forms of certain pediatric cancers, for example, investigators from other institutions have their sights set on primary, metastatic, and treatment-resistant adult tumors.

Because the roots of cancer development can take hold long before a malignant tumor is diagnosed, the investigators reasoned that it may be possible to tease out details of this trajectory by profiling the morphology, genomics, epigenetic regulators, and other features in the tumor; the tumor microenvironment; and even non-cancerous tissues that may transition to cancer.

In particular, there has been growing interest in understanding the early changes in samples that have not yet become cancerous. The HTAN team includes researchers from the Pre-Cancer Atlas Pilot Project, and five of the participating HTAN centers are set to focus on the pre-cancer side of the equation.

The project will also focus on cells stemming from full-blown tumors that did or did not respond to treatment, or that developed resistance after some initial responsiveness, the team explained. In the process, the authors suggested, the HTAN project "will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types."

Beyond the potential for using the atlases for better understanding cancer biology and treatment strategies, the authors proposed that HTAN datasets may eventually lead to enhanced cancer diagnostic and monitoring methods.

"The network will provide protocols, software, and best-practice guidelines to promote the development and deployment of technologies that we believe will have a profound impact on the study of human tumors, including open standards in histology and histopathology," they wrote, noting that "HTAN's collaborative nature will establish a model within our scientific community for the integration of efforts and data."