Integrative Research Centers
Dana-Farber/Brigham and Women's Center for Molecular Oncologic
Pathology
Massimo Loda, MD, Keith Ligon, MD, PhD, and Matthew Theisen As cancer treatment approaches an era of personalized medicine,
in which care is tailored to the molecular traits of a person's
tumor, success will depend on discovering distinct genetic
signatures within cancer cells. The Center for Molecular Oncologic
Pathology was created to advance collaborative pathology-based
research projects that have the potential to result in applications
for targeted cancer therapy. To achieve this end, the Center brings
together faculty from Dana-Farber and Brigham and Women's Hospital
with molecular oncologic pathology expertise to advance
pathology-based, hypothesis-driven research. The Center also
develops novel diagnostic and prognostic tests by enabling
researchers to apply their knowledge of the molecular biology of
cancer to pathology.
Currently, the Center is pioneering the development of
quantum-dot immunohistochemistry and FISH by coupling
oligonucleotide probes with fluorescent nanoparticles. The probes
chosen represent molecular signatures previously identified by gene
expression arrays and yield new ways of diagnosing and predicting
tumor progression at initial biopsy. The Center has utilized
phosphoprotein immunohistochemistry to detect proteins that are
active in pathways driving tumor initiation and progression,
allowing prediction of patient response to kinase inhibitor
therapy. Furthermore, it has developed an ex-vivo, short-term,
culture model system. This system allows for pharmacodynamic
profiling of a patient's tumor with preclinical prediction of
response to chemotherapy. It has also generated xenograft mouse
models, derived from resected primary organ-confined human tumors,
that now serve as models for gene discovery or drug testing. These
tools will ultimately be translated into diagnostic clinical
assays, thereby providing the means to improve therapy selection
for cancer patients.