# Investigating the contribution of cellular senescence to the efficacy of radiation therapy.

> **NIH NIH K08** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $255,045

## Abstract

PROJECT SUMMARY/ ABSTRACT
Ionizing radiation (IR), a highly effective cancer therapy, is known to induce cellular senescence, a cell cycle
arrest program triggered by the DNA damage response. Cellular senescence results in upregulation of mRNAs
encoding secreted factors (including inflammatory cytokines and chemokines), a program referred to as the
senescence-associated secretory phenotype (SASP). The SASP modulates the tumor microenvironment, and
it has pleiotropic immune-modulatory effects. Although IR sensitivity is known to depend upon host immunity,
the contribution of senescence and the resultant SASP is unknown. Our preliminary data suggest that the
SASP contributes to both localized and systemic anti-tumor effects of IR in immunocompetent, but not
immunodeficient, mouse models. Thus, we hypothesize that the anti-tumor effects of IR, both local and
systemic, are mediated in part by the SASP through an immune effector. This project will use a combination of
mouse and human models to test this hypothesis and to define the mechanisms through which the radiation-
induced SASP alters both local and distant tumor microenvironments. In addition, it will use patient tumor
samples to establish clinical relevance in patients with rectal cancer treated with radiation therapy or with
radiation combined with immune checkpoint blockade. While this proposal focuses on rectal cancer, it has
broad clinical implications, as radiation therapy is a widely used treatment modality for cancer. Dr. Paul
Romesser has outlined a 5-year career plan that builds upon his clinical training in radiation oncology and on
his research background in cancer biology, radiation biology, genetically engineered mouse models, and
patient-derived models. Dr. Romesser will be mentored by Dr. Scott Lowe, an internationally renowned expert
in senescence, p53 biology, and mouse modeling with a strong track record of training physician-scientists. Dr.
Romesser’s career development plan includes research experience, course work, workshops, and mentoring
from an interdisciplinary advisory committee comprising distinguished basic scientists, physician-scientists, and
radiation oncologists. He will have the support and infrastructure of Memorial Sloan Kettering Cancer Center, a
center of excellence in basic, translational, and clinical cancer research. Successful completion of the research
project will lead to new approaches for treating patients with radiation therapy and will provide the foundation
for Dr. Romesser to transition to a position as an independent investigator with his own laboratory and R01
funding.

## Key facts

- **NIH application ID:** 10911843
- **Project number:** 5K08CA255574-04
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Paul Bernard Romesser
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $255,045
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911843

## Citation

> US National Institutes of Health, RePORTER application 10911843, Investigating the contribution of cellular senescence to the efficacy of radiation therapy. (5K08CA255574-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10911843. Licensed CC0.

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