# Blood-based biomarker of therapeutic efficacy for mesothelioma

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2020 · $408,829

## Abstract

PROJECT SUMMARY
Patients with mesothelioma urgently need improved strategies to monitor treatment responses with systemic
therapy and to detect early recurrence of disease after surgery. The growth patterns of mesothelioma and the
therapeutic changes associated with its treatment limit the utility of imaging for these patients. Mesothelioma is
a spatially complex disease that thickens along the pleura in circumferential sheets around the lungs. Standard
imaging criteria used to assess treatment response were not designed with this malignancy in mind. Tumor
measurements cannot be accurately made adjacent to non-malignant tissue such as the diaphragm or
atelectasis or next to inflammation or scarring that result from common treatments such as surgery or talc
pleurodesis. Whereas mesothelioma has very few nonsynonymous point mutations, we have discovered that
large chromosomal rearrangements detected by Mate-Pair sequencing (MPseq) are common in this disease.
Conventional sequencing approaches do not readily detect these rearrangements. In our preliminary data we
show how these rearrangements can be detected in blood as cell-free tumor DNA (ctDNA). The objectives of
our proposal are to optimize the selection of chromosomal rearrangements for detection in blood as ctDNA,
and to determine whether longitudinal changes in cell-free chromosomal rearrangements correlate with
imaging-based standards of response assessment for patients with mesothelioma. Our central hypothesis is
that chromosomal rearrangements can be detected as ctDNA and that their changes will correlate with
conventional radiographic criteria of response. We will test our working hypothesis by using the approach of
prospective, correlative biomarker studies with the following two specific aims: (1) determine the extent to
which circulating tumor chromosomal rearrangements can be detected in patients with newly diagnosed
mesothelioma and (2) determine the extent to which the dynamics of chromosomal rearrangement ctDNA
correlate with response to systemic chemotherapy as defined by conventional radiologic criteria. This approach
is highly innovative because the low number of single nucleotide variants in mesothelioma precludes the use of
commercial ctDNA assays for patients with this disease. Our preliminary data suggest that with optimization,
the use of cell-free chromosomal rearrangements will overcome the limited sensitivities of other cell-free DNA
tests for mesothelioma and provide a blood-based biomarker of therapeutic efficacy. This proposed research is
significant because the successful completion of our study would improve upon our standards of care for
disease monitoring and response assessment. Additionally, the use of chromosomal rearrangement ctDNA as
a real-time biomarker of therapeutic efficacy could be incorporated into clinical trials to help physicians select
the patients at highest risk of recurrence to receive systemic therapy while sparing toxicities in those who are
a...

## Key facts

- **NIH application ID:** 10031018
- **Project number:** 1R21CA251923-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Aaron Scott Mansfield
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $408,829
- **Award type:** 1
- **Project period:** 2020-07-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10031018

## Citation

> US National Institutes of Health, RePORTER application 10031018, Blood-based biomarker of therapeutic efficacy for mesothelioma (1R21CA251923-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10031018. Licensed CC0.

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