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Cancer Biology

Cancer is a complex group of related diseases characterized by uncontrolled cell proliferation and metastasis to other parts of the body. These changes are driven by mutations that disrupt normal gene expression and protein function, altering metabolism, and increasing proliferative and metastatic potential. New therapies are desperately needed.
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Our Approach to Cancer Research

Scientists in CRI are expanding our understanding of cancer and working to find new therapies using five main approaches.

Many cancers arise from the inappropriate activation of the self-renewal mechanisms that normally regulate the maintenance of normal stem cells. By comparing the processes by which stem cells and cancer cells replicate, CRI scientists are improving our understanding of these mechanisms and determining if their inhibition can be used therapeutically.

CRI scientists are using genetically engineered mouse models, patient-derived xenografts, and cultured organoids. Each approach has advantages and disadvantages, and these multi-faceted strategies are allowing CRI scientists to tackle fundamental problems in cancer biology. 

Cancer cells reprogram metabolic pathways to proliferate and metastasize. Understanding how these metabolic activities are altered in cancer is a key step toward developing new treatments to selectively inhibit cancer growth. 

CRI scientists study the mechanisms that allow cancer cells to spread beyond their sites of origin. Therapeutics that target these mechanisms could block cancer progression.

Studying genetic alterations in cancer, including gene amplifications, mutations, and deletions reveals new insights into the regulation of cancer development, progression, and therapy resistance.

Cancer Research Faculty

Michalis Agathocleous, Ph.D.

Developed approaches to study the metabolism of rare cell types and discovered cell type specific metabolic requirements for hematopoietic and leukemia cells.

Ralph DeBerardinis, M.D., Ph.D.

Pioneered the use of stable isotope tracers in cancer metabolism research, defining many new metabolic pathways and liabilities in human cancer.

Gerta Hoxhaj, Ph.D.

Deciphered mechanisms by which cancer cells rewire their metabolism to promote anabolic growth and sustain redox homeostasis.

Sam McBrayer, Ph.D.

Created mouse and human-derived models of brain tumors and used them to discover targetable metabolic vulnerabilities.

Sean Morrison, Ph.D.

Discovered that oxidative stress limits the survival of some cancer cells during metastasis and identified approaches to develop pro-oxidant therapies that inhibit cancer progression.

Sihan Wu, Ph.D.

Defined physical shape and molecular function of extrachromosomal DNA in cancer.

Hao Zhu, M.D.

Defined mechanisms that regulate tissue injury, regeneration, and cancer development in the liver.

Featured Cancer Discoveries

Cancer Biology, Metabolism
August 2024

Kidney cancers rely on mitochondrial metabolism to metastasize

DeBerardinis lab: Discovered that contrary to how tumors operate while still in the kidney, metastatic kidney cancers rely heavily on mitochondrial metabolism. The mitochondrial electron transport chain is much more active in tumors that have metastasized than in tumors still growing in the kidney. Nature 633, 923-31
Cancer Biology, Metabolism
July 2024

Tumor growth fueled by nucleotide salvage

Hoxhaj lab: Cancer cells salvage purine nucleotides to fuel tumor growth, including purines in foods we eat, an important discovery with implications for cancer therapies. CRI researchers challenged the long-standing belief that tumors primarily acquire purine nucleotides – building blocks for DNA, which is required for cellular growth and function – by constructing them from scratch via de novo synthesis. Research also shows tumors significantly use the more efficient salvage, or recycling, pathway to acquire purines. Cell 187, 3602-18
Cancer Biology
May 2024

Small cell lung cancer acquires cross-resistance due to extrachromosomal DNA amplification of MYC paralogs

Wu Lab: Small cell lung cancer is initially chemosensitive, but acquired cross-resistance renders this disease refractory to further treatment and ultimately fatal. CRI researchers & colleagues used a population of PDX models to discover that amplifications of MYC paralogs on ecDNA are recurrent drivers of acquired cross-resistance in SCLC. Cancer Discovery 14, 804-827
Cancer Biology
April 2023

The presence of extrachromosomal DNA can accelerate cancer formation

Wu lab: Extrachromosomal DNA (ecDNA) found to harbor cancer-associated oncogenes and immunomodulatory genes that promote cancer development in pre-cancerous cells. These findings raise the possibility of earlier interventions and preventive measures for patients with tumors containing ecDNA and provide a new understanding of ecDNA’s role in cancer development. Nature 616, 798-805
Cancer Biology, Genetics
August 2022

Researchers identify new druggable therapeutic pathway in a deadly form of brain cancer

McBrayer lab: Discovered that mutations in IDH genes, which are common in adult and adolescent brain tumors, cause cells to become addicted to a metabolic process called de novo pyrimidine nucleotide synthesis. This addiction stems from the ability of IDH mutations to increase susceptibility to DNA damage, which provides new insights into the ways that these mutations reprogram brain cell biology. Cancer Cell 40, 939-956
Cancer Biology
August 2020

Lymph protects metastasizing melanoma cells from ferroptosis

Morrison lab: Discovered that melanoma cells tend to metastasize through lymphatics because the lymphatics protect melanoma cells from oxidative stress, which kills most melanoma cells that attempt to metastasize through the blood by inducing ferroptosis, a form of cell death marked by lipid oxidation. Nature 585, 113-118
Cancer Biology
December 2019

CRI scientists discover metabolic feature that allows melanoma cells to spread

Morrison lab: Found certain melanoma cells are more likely to spread through the body. Efficiently metastasizing melanoma cells take up more lactate because they have higher levels of a lactate transporter, called monocarboxylate transporter 1 (MCT1), on their cell surface as compared with inefficient metastasizers. This demonstrates that metabolic differences among melanoma cells confer differences in metastatic potential. Nature 577, 115-120
Cancer Biology
October 2015

Antioxidant use may promote spread of cancer

Morrison lab: Found antioxidants promote the survival of cancer cells during metastasis. These results raised the possibility that cancer should be treated with pro-oxidants rather than antioxidants and explained why administration of antioxidants to patients led to worse outcomes in clinical trials. Nature 527, 186-91
See All Discoveries

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