Primary Patient-Derived Cancer Cells and Their Potential for Personalized Cancer Patient Care

Cell Rep. 2017 Dec 12;21(11):3298-3309. doi: 10.1016/j.celrep.2017.11.051.

Abstract

Personalized cancer therapy is based on a patient's tumor lineage, histopathology, expression analyses, and/or tumor DNA or RNA analysis. Here, we aim to develop an in vitro functional assay of a patient's living cancer cells that could complement these approaches. We present methods for developing cell cultures from tumor biopsies and identify the types of samples and culture conditions associated with higher efficiency of model establishment. Toward the application of patient-derived cell cultures for personalized care, we established an immunofluorescence-based functional assay that quantifies cancer cell responses to targeted therapy in mixed cell cultures. Assaying patient-derived lung cancer cultures with this method showed promise in modeling patient response for diagnostic use. This platform should allow for the development of co-clinical trial studies to prospectively test the value of drug profiling on tumor-biopsy-derived cultures to direct patient care.

Keywords: NSCLC; patient-derived cancer cells; personalized medicine.

MeSH terms

  • Acrylamides
  • Aminopyridines
  • Anaplastic Lymphoma Kinase
  • Aniline Compounds
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • Crizotinib
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride / therapeutic use
  • Feeder Cells / cytology
  • Fluorescent Antibody Technique / methods
  • Gene Expression
  • High-Throughput Screening Assays
  • Humans
  • Keratin-18 / genetics
  • Keratin-18 / metabolism
  • Keratin-8 / genetics
  • Keratin-8 / metabolism
  • Lactams
  • Lactams, Macrocyclic / therapeutic use
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mutation
  • Neoplasms / classification
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Piperazines / therapeutic use
  • Precision Medicine / methods*
  • Primary Cell Culture / methods*
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Tumor Cells, Cultured

Substances

  • Acrylamides
  • Aminopyridines
  • Aniline Compounds
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Keratin-18
  • Keratin-8
  • Lactams
  • Lactams, Macrocyclic
  • Piperazines
  • Pyrazoles
  • Pyridines
  • osimertinib
  • Crizotinib
  • Erlotinib Hydrochloride
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • lorlatinib