Generation of Human Tumor Atlases

Cancer development, growth (progression), and spread (metastasis) require complex interactions within the tumor microenvironment that are mediated by many factors. Although researchers have made progress in understanding these interactions and their role in cancer processes, a great deal is still unknown about the architecture of precancerous lesions and tumors. In particular, little is known about how the biology of and interactions within a tumor change over time and in response to cancer treatments.

This recommendation focuses on generating human tumor atlases that describe the cellular, structural, and molecular characteristics of human cancers over time. Tumor atlases aim to reveal processes that cause malignancy by characterizing tumors and the tissues and cells around them from a diverse population of people with cancer. Additionally, there is a need for tumor atlases that map multiple stages in cancer progression, ranging from precancerous lesions to advanced cancer metastases.

The ultimate goal of this recommendation is to enable predictive modeling of how cancers develop and respond to treatment in different populations. This modeling will be used to advance the understanding of cancer biology and refine treatment choices for patients.

NCI has awarded funding to the following research project that aligns with this recommendation's goal to generate human tumor atlases.

Human Tumor Atlas Network (HTAN)

HTAN is a collaborative network that is constructing 3-dimensional atlases of the cellular, morphological, and molecular features of human cancers over time. The network is generating atlases representing a diverse population of people with cancer, including minority and underserved patients of all ages with different cancer types and stages of disease, as well as individuals with high-risk hereditary tumors.

Additionally, the atlases being created by the network describe important changes during cancer progression, such as the transition of pre-malignant tumors to malignant tumors, the progression to metastatic cancer, the response to cancer treatment, and the development of resistance to treatment.

Highlights of HTAN Research Progress

The HTAN Research Centers are focused on understanding the behaviors of tumors at every stage of progression, from precancerous conditions to advanced cancers, for different organs. The HTAN centers have developed innovative imaging and sequencing technologies, computational analysis tools, and resources to build detailed, single-cell resolution atlases. For example, several HTAN centers have used a highly multiplexed immunofluorescence technology to show single-cell data in the context of the original spatial arrangement of the tissue. They used the technology to analyze interactions between different cell types, such as between tumor cells and immune cells in the tumor microenvironment.

The HTAN Data Coordinating Center manages the data storage, sharing, and compilation of the atlases constructed by the network. Data and metadata that accompany the first HTAN atlases are available through the HTAN Data Portal, allowing the broader research community to use and integrate HTAN data with their own data and research.

In the spring of 2021, data from eight initial atlases representing seven tumor types were added to the data portal in a coordinated publication and release. This included single-cell and bulk sequencing data, digital pathology data, highly multiplexed protein-based imaging data, and extensive clinical data from several hundred tumor samples, ranging from precancers to metastatic lesions.

The comprehensive human tumor atlases that are being created by HTAN will accelerate the biological understanding of cancer and clinical decisions for the care of cancer patients.

More information about the network can be found on the HTAN website and on Twitter at @NCIHTAN.

Human Tumor Atlas Projects Awarded Cancer Moonshot Funding

Awarded Projects
Funding Opportunity Project Title Institution Principal Investigator(s)
Human Tumor Atlas Network: Data Coordinating Center (U24) Human Tumor Atlas Network: Data Coordinating Center Dana-Farber Cancer Institute Cerami, Ethan;  Thorsson, Vésteinn; Schultz, Nikolaus
Human Tumor Atlases (HTA) Precancer Atlas Research Centers (U2C) Integrative Single-Cell Atlas of Host and Microenvironment in Colorectal Neoplastic Transformation Vanderbilt University Coffey, Robert J; Lau, Ken Siu Kwong; Shrubsole, Martha J
Breast Pre-Cancer Atlas Center Duke University Hwang, Eun-Sil Shelley; Maley, Carlo; West, Robert B
Precancer Atlas of Familial Adenomatous Polyposis Stanford University Snyder, Michael P; Ford, James M
Pre-cancer Atlases of Cutaneous and Hematologic Origin (PATCH Center) Harvard Medical School Sorger, Peter Karl; Aster, Jon C; Santagata, Sandro
The Lung PCA: A Multi-Dimensional Atlas of Pulmonary Premalignancy Boston University Medical Campus Spira, Avrum E; Dubinett, Steven M
Human Tumor Atlases (HTA) Research Centers (U2C) Washington University Human Tumor Atlas Research Center Washington University Ding, Li; Achilefu, Samuel; Fields, Ryan C; Gillanders, William E
Omic and Multidimensional Spatial Atlas of Metastatic Breast and Prostate Cancers Oregon Health & Science University Goecks, Jeremy; Mills; Gray, Joe W;  Mills, Gordon B
The Cellular Geography of Therapeutic Resistance in Cancer Dana-Farber Cancer Institute Johnson, Bruce; 
Transition to Metastatic State: Lung Cancer, Pancreatic Cancer and Brain Metastasis Sloan-Kettering Institute for Cancer Research Pe'er, Dana; Iacobuzio-Donahue, Christine A
Center for Pediatric Tumor Cell Atlas Children's Hospital of Philadelphia Tan, Kai; Hunger, Stephen Patrick
National Cancer Institute Program Project Applications (P01) Integrative Oncogenomics of Multiple Myeloma Dana-Farber Cancer Institute Munshi, Nikhil C