Human Tumor Atlases Provide Important Insights into How Cancer Tumors Develop and Spread

In 2018, NIH’s National Cancer Institute launched a research initiative called the Human Tumor Atlas Network (HTAN) to construct detailed, three-dimensional maps of human tumors including their underlying cellular, molecular, and spatial features to better understand cancer biology. I’m pleased to share progress toward this goal through an impressive collection of HTAN studies that elucidate how tumors of various types develop, respond to treatment, and recur.

Several of these studies, reported in the Nature portfolio of journals, offer key insights into the role of a tumor’s immediate surroundings and the immune system in encouraging cancer’s spread and resistance to treatment. They map the molecular and cellular features underlying the transformation of precancerous lesions into cancerous tumors and other important cancer transitions. Other studies describe innovative technologies and analytical tools that may be applied to the new findings, as well as many other datasets and studies.

HTAN is supported by the Cancer Moonshot℠ , a bold effort to accelerate scientific discovery in cancer research. The studies were made possible through the work of many researchers at ten research centers across the country. Together, they developed and implemented the tools needed to capture, analyze, and visualize complex data representing the molecules, cells, and tissues within diverse tumors over time. Here are some highlights:

• One study examined the interactions among cancer and non-cancer cells in breast, colon, pancreas, kidney, uterus, and bile duct cancers. The study team used RNA sequencing within single cells to describe tumor structures and define spatially distinct cancer cell clusters or “microregions.” They also used powerful imaging technologies to reconstruct 3D tumor structures to provide insight into the ways tumors are organized.

• Another study in colorectal cancer mapped differences between normal colon tissue, primary cancer tissue, and metastatic tissue to identify changes that drive colorectal cancer’s progression and transition from a primary tumor to metastatic disease.

• Two other studies (here and here ) also focused on colorectal cancer to define early molecular-level events that drive the transformation of precancerous lesions in the colon into cancer.

• Another study profiled 93 samples, including healthy, precancerous, and cancerous tissue, from six people with familial adenomatous polyposis, a genetic condition that causes people to develop hundreds of precancerous polyps in the colon, which increases the risk for colorectal cancer. Studies like this not only provide insight into this condition but are also considered ideal models for exploring the transition from early precancerous states to colorectal cancer.

• Two studies in the collection focus on breast cancer. One of these uses single-cell RNA sequencing to profile metastatic cancer from 60 individuals with this disease, while another describes the underlying genetic networks that define breast cancer subtypes based on profiles of thousands of cells from each of 37 tumors.

These studies expand upon the first tumor atlas studies reported in 2020 and 2021. Together, they represent a comprehensive, publicly available resource that will enable cancer researchers in the U.S. and around the world to better understand cancer development and progression, with implications for advancing cancer treatment and prevention.

Reference:

The Human Tumor Atlas Network (HTAN): exploring tumor evaluation in time and space. Nature. (Collection of studies ) 2024.

NIH Support: National Cancer Institute