Creating an Atlas to Map the Progression of Rare Childhood Cancers
Scientists don’t understand how solid tumors like Neuroblastoma, Wilm’s Tumor and Rhabdomyosarcoma resist therapies and recur. Researchers at the Cancer and Blood Disease Institute of Children’s Hospital Los Angeles are part of a collective working to change that.
Shahab Asgharzadeh, MD, Director of CHLA’s Neuroblastoma Basic and Translational Program, and Cancer and Blood Disease Institute Director James Amatruda, MD, PhD, along with collaborator Long Cai, PhD, Professor of Biology and Biological Engineering at Caltech, are mapping the stages of the molecular and cellular conditions that contribute to tumor cells becoming resistant, with a focus on the non-cancerous cells—such as immune cells—that aid in this process and ultimately lead to the recurrence of cancers.
The researchers were awarded a U01 grant for $5,678,350 from the National Cancer Institute to develop the Pediatric Solid Tumor Microenvironment Atlas. This initiative will document the role of the tumor microenvironment in therapy resistance and recurrence of these three rare and aggressive cancers. In this collaboration, CHLA will provide annotated tumor specimens from an ethnically diverse population and generate innovative spatial biology data. The CalTech group will also contribute to spatial technologies and novel data science approaches to analyze the data.
Mapping the microenvironment
“Understanding the role of benign cells such as immune cells in supporting the tumor cells that resist therapy is an important step toward personalized care,” says Dr. Asgharzadeh. “This atlas—a map of the tumor microenvironment of these specific cancers—will help us to uncover basic and acquired mechanisms of resistance to therapies and find targetable vulnerabilities driven by resistance in the tumor microenvironment. This atlas will also collect information on how these rare pediatric cancers affect minority and underserved populations, who are often neglected in genetic studies. This data will be available to researchers and clinicians around the country.”
The 10 research centers of the Human Tumor Atlas Network (HTAN), part of the National Cancer Institute-funded Cancer Moonshot initiative, will create virtual three-dimensional atlases of the dynamic cellular, structural and molecular features of human cancers as they evolve from precancerous lesions to advanced disease. These atlases aim to define the critical processes and events in the evolution of diverse human cancers, charting the transition of pre-malignant lesions to malignant tumors and to metastatic cancer as well as tumor response to therapeutics and the development of therapeutic resistance.
“There is an urgent need to improve the survival of patients with high-risk subtypes of these pediatric cancers and to decrease treatment-related illness,” says Dr. Amatruda. “By delving deep into the tumor microenvironment and its impact on treatment response, we aim to advance our understanding of pediatric solid tumors to find more effective therapeutic strategies for these childhood cancers.”
