# MICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALS

> **NIH NIH U01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $1,396,406

## Abstract

Gene expression-based approaches to breast cancer are largely for prognostication, not prediction of
individual drug responses. Furthermore, there are still no clinically validated somatic mutation-based
approaches in breast cancer management based on next generation DNA sequencing (NGS). A major
obstacle to progress in NGS-based diagnostics is a fundamental one: we poorly understand how complex
cancer somatic genomes drive clinical phenotypes and drug vulnerabilities. Key issues such as therapeutic
resistance, the contribution of the tumor microenvironment and the metastatic process belie single
gene/mutation explanations. The new field of proteogenomics provides an opportunity to generate new
insights by melding the complexity of cancer genomics with cancer proteomics to more completely understand
how somatic genomes activate aberrant signal transduction events that drive cancer pathogenesis.
To this end, we have formed a multi-institutional, multi-omics center to engage in collaborative studies under
the aegis of the NCI-CPTAC PTRC initiative. Our core builds upon ongoing collaborations between the highly
experienced and innovative teams at Baylor College of Medicine and the Broad Institute with complementary
strengths in cancer genomics, precision diagnostics, proteogenomic technologies and decades of experience
in breast cancer research.
Our proposal leverages state-of-the-art quantitative discovery proteomics and phosphoproteomics as well as
targeted assays to measure the kinome and chromatin modifications. These sensitive and reproducible
pipelines will be used to analyze preclinical models, well-annotated cohorts and clinical trial samples in an
iterative design. A robust proteogenomics pipeline developed by our group will be used to analyze and
visualize the data. These analyses, together with the primary data generated by this multidisciplinary proposal
will be made rapidly available to the scientific community. While the FOA envisioned that only targeted
approaches could be applicable in the Clinical Research Arm, it did not anticipate the major advances already
well underway in discovery proteomics. We show that the global, discovery-based proteome and
phosphoproteome pipeline we have developed is already applicable to biopsy-scale tumor samples, providing
deep and broad quantitative coverage of the proteome and phosphoproteome with excellent reproducibility and
robustness. This key conceptual and practical advance enables us to employ discovery and targeted
approaches in both Preclinical and Clinical arms thereby greatly increasing the power of our proposed studies
to generate impactful insight into the causes of breast cancer mortality.
We postulate that this integrated approach will provide new understanding of the biology of response and
resistance to chemotherapeutics, sounder therapeutic hypotheses and identify more accurate predictive
biomarkers for drug resistance and treatment selection that could be developed and deployed as...

## Key facts

- **NIH application ID:** 10170307
- **Project number:** 5U01CA214125-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Meenakshi Anurag
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,396,406
- **Award type:** 5
- **Project period:** 2017-06-07 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170307

## Citation

> US National Institutes of Health, RePORTER application 10170307, MICROSCALED PROTEOGENOMICS FOR CANCER CLINICAL TRIALS (5U01CA214125-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10170307. Licensed CC0.

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