Poly-ligand profiling differentiates trastuzumab-treated breast cancer patients according to their outcomes

Autor: Valeriy Domenyuk, Adam Stark, Jie Wang, Richard Greil, Xixi Wei, David Spetzler, Symon Levenberg, Jeffrey L. Vacirca, Michael Famulok, Nianqing Xiao, Zoran Gatalica, Simon Peter Gampenrieder, Daniel Magee, David D. Halbert, Radhika Santhanam, John Quackenbush, Guenter Mayer, Gabriel Rinnerthaler, Patrick Kennedy, Brandon Toussaint, Mark R. Miglarese, George Poste, John L. Marshall, Donald A. Berry, Lee S. Schwartzberg, Anna D. Barker, Andreas Voss, Gregory A. Vidal, Amy B. Heimberger
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
General Physics and Astronomy
Kaplan-Meier Estimate
Ligands
0302 clinical medicine
Antineoplastic Agents
Immunological
Trastuzumab
Antineoplastic Combined Chemotherapy Protocols
Precision Medicine
lcsh:Science
Aged
80 and over
Multidisciplinary
SELEX Aptamer Technique
Middle Aged
Gene Expression Regulation
Neoplastic
Phenotype
Treatment Outcome
Drug development
030220 oncology & carcinogenesis
Area Under Curve
Disease Progression
Female
medicine.drug
Adult
medicine.medical_specialty
Science
DNA
Single-Stranded
Breast Neoplasms
General Biochemistry
Genetics and Molecular Biology
Patient care
Article
Disease-Free Survival
03 medical and health sciences
Breast cancer
Text mining
Internal medicine
medicine
Biomarkers
Tumor
Humans
Aged
business.industry
General Chemistry
Sequence Analysis
DNA
medicine.disease
Precision medicine
Clinical trial
030104 developmental biology
Precision oncology
lcsh:Q
business
Zdroj: Nature Communications
Nature Communications, Vol 9, Iss 1, Pp 1-9 (2018)
Popis: Assessing the phenotypic diversity underlying tumour progression requires the identification of variations in the respective molecular interaction networks. Here we report proof-of-concept for a platform called poly-ligand profiling (PLP) that surveys these system states and distinguishes breast cancer patients who did or did not derive benefit from trastuzumab. We perform tissue-SELEX on breast cancer specimens to enrich single-stranded DNA (ssDNA) libraries that preferentially interact with molecular components associated with the two clinical phenotypes. Testing of independent sample sets verifies the ability of PLP to classify trastuzumab-treated patients according to their clinical outcomes with ROC-AUC of 0.78. Standard HER2 testing of the same patients gives a ROC-AUC of 0.47. Kaplan–Meier analysis reveals a median increase in benefit from trastuzumab-containing treatments of 300 days for PLP-positive compared to PLP-negative patients. If prospectively validated, PLP may increase success rates in precision oncology and clinical trials, thus improving both patient care and drug development.
Patients’ selection is particularly important in cancer treatment. Here the authors present a proof-of-principle methodology that could be potentially important in assisting therapeutic decisions in the treatment of breast cancer patients.
Databáze: OpenAIRE
Externí odkaz: