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Research Advances from Translational and Basic Science Research in Early Lesions (TBEL)

TBEL investigators are advancing cancer interception science by defining the biological changes that distinguish precancerous lesions/early cancers from cancer/invasive disease. They are also developing tools to detect these changes at the earliest and least life-threatening stages of the disease as possible. 

Mechanisms of Precancer Development and Progression

Researchers supported by the MD Anderson TBEL Center revealed that loss of NADPH-producing enzymes promotes the formation of pancreatic precancerous lesions in preclinical models. According to Dr. Costas Lyssiotis (co-lead investigator of the study), “Our study can help the search for new biomarkers that can intercept pancreatic cancer before it progresses.”

Using single-cell RNA sequencing and molecular pathology, investigators with the Johns Hopkins University TBEL Center found that MYC activation in neoplastic cells reprograms the prostate cancer microenvironment. The findings showed that increased MYC signaling creates a pro-inflammatory microenvironment at the precancerous stage, which transitions to an immunosuppressive state during the progression to invasive carcinoma. 

Researchers with the Fred Hutch TBEL Center showed that colorectal cancer-associated bacteria are broadly distributed in global microbiomes and drivers of precancerous change. According to the authors of the study, the findings "demonstrate that the microbiome can drive precancer states, thereby potentially revealing novel cancer prevention opportunities."

Technology Development

Researchers with the Houston Methodist Research Institute TBEL Center developed a urine-based multi-marker panel for bladder cancer detection across multiple longitudinal cohort studies. This study showed that molecular signals could potentially help identify bladder cancer before diagnosis and reduce the need for invasive procedures (such as cystoscopy).

Investigators with the Vanderbilt University TBEL Center created MEcell, a microenvironment aware spatial omics method to improve the identification of spatially defined cell states. This approach could improve the study of precancers by enabling more accurate determination of spatially and microenvironmentally influenced cell identities, including how interactions between emerging abnormal cells and their surrounding tissue may contribute to precancer development and progression.

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