# Reverse transcriptase inhibitor effects on the mobilome of colon cancer

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $577,473

## Abstract

PROJECT SUMMARY
Large scale transcriptional analysis with RNA-sequencing has revealed the abundant expression of repetitive
element RNAs in cancers compared to normal tissues. Moreover, many of these repeat RNAs are capable of
retrotransposition through reverse transcription (RT), which leads to alterations in the cancer genome. Our
preclinical cell line and mouse models have demonstrated the ability of these endogenous RT to be blocked by
nucleoside reverse transcriptase inhibitors (NRTIs) commonly used for viral infections. Interestingly, we have
found anti-cancer effects of NRTIs in multiple colorectal cancer (CRC) cell lines grown in 3D tumor spheres and
in mouse xenografts in vivo. This led to the initial of a Phase II clinical trial of the NRTI 3TC in metastatic CRC
patients where pre- and post-treatment biopsies are being obtained for correlative science research.
The Ting lab has expertise in cell line and animal models to study NRTI effects in CRC and the sequencing and
RNA in situ hybridization methods to quantify repeat elements in these systems. The Greenbaum lab has
developed computational tools to characterize repeat RNA expression and their effects on innate immunity. The
Park lab has pioneered the tools to study DNA retrotransposition events in cancer genomes. The combined
expertise and tools generated to study repeat RNAs by the Ting, Greenbaum, and Park labs uniquely positions
us to execute the goals of this project.
We plan to:
1) Understand the effects of 3TC on cellular response and repeat RNA expression in CRC model systems
2) Characterize the effect of 3TC on repeat retrotransposition in xenograft models
3) Evaluate repeat RNA expression, retrotransposition, and the tumor immune microenvironment from patient
biopsies obtained from CRC patients treated with 3TC

## Key facts

- **NIH application ID:** 10215256
- **Project number:** 5R01CA240924-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Benjamin Greenbaum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $577,473
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215256

## Citation

> US National Institutes of Health, RePORTER application 10215256, Reverse transcriptase inhibitor effects on the mobilome of colon cancer (5R01CA240924-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10215256. Licensed CC0.

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