project-idea

ChemoSense TNBC: A Pre-Treatment Biomarker Screener for Triple-Negative Breast Cancer Chemoresistance

Pre-treatment biopsies from TNBC patients show distinct proteomic and metabolomic signatures — particularly SIRT5 overexpression — that predict de novo chemoresistance before a single dose of treatment is given.

The ability to predict chemotherapy resistance before treatment starts is one of the most clinically valuable applications of translational cancer research. ChemoSense TNBC would be a bioinformatics tool and clinical decision support concept that scores pre-treatment TNBC biopsies for chemoresistance risk based on the biomarker signature from this paper — SIRT5 expression, OXPHOS pathway activity, and nucleotide metabolism markers.

The tool would take normalized proteomic or RNA-seq data from a pre-treatment biopsy and output a resistance risk score with a confidence interval, along with a visual report showing how the patient's tumor compares to the training cohort on key features. A secondary output would flag patients with high SIRT5/OXPHOS signatures as potential candidates for ATR inhibitor combination studies — since this paper also links SIRT5-driven resistance to ATR checkpoint dysregulation.

Building an initial prototype using publicly available TNBC datasets (TCGA, METABRIC, I-SPY clinical trial data) to validate the SIRT5 signature would establish proof-of-concept and create the foundation for a prospective clinical validation study. This directly addresses an actionable gap: TNBC patients currently receive empirical chemotherapy with no pre-treatment resistance prediction tool available in routine care.

Who Is This For?

Breast oncologists, translational cancer researchers, and bioinformaticians at academic cancer centers with access to pre-treatment TNBC biopsy data.

Skills & Tools Needed

Bioinformatics (proteomics/RNA-seq normalization and analysis)
Machine learning for clinical biomarker models
Survival analysis and clinical outcome modeling
Clinical report design
TCGA/METABRIC data access and analysis

Feasibility

medium — Public TNBC datasets provide a validation path, but clinical deployment requires prospective validation in an independent cohort — a significant regulatory and resource hurdle.

Inspired by: A SIRT5-induced metabolic switch underlies chemoresistance and ATR checkpoint dependence in triple-negative breast cancer

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