1. MGH, Collaborative interactions
Collaboration has facilitated dissemination of the link between DNA polymorphisms and gastrointestinal toxicity in patients with non-small-cell lung cancer treated with chest radiotherapy and chemotherapy.
A hospital-based case-control series of more than 2,000 patients and controls required close collaboration with the surgical team from the MGH and the medical oncology group; the goal of this series was to determine the impact of germline polymorphisms on the risk of developing cancer.
A recent addition to these studies has been assessing genetic polymorphisms in the DNA repair enzymes and their association with survival and gastrointestinal toxicity when patients are treated with chemotherapy and/or chest radiotherapy.
2. Molecular Epidemiology Laboratory—MGH and HSPS, Collaborative interactions
The Molecular Epidemiology Laboratory, along with members of the clinical sciences portion of the Lung Cancer Program at MGH, are working toward identifying additional polymorphisms within DNA repair enzymes and aromatic hydrocarbon metabolizing enzymes, with plans to expand these studies to the Longwood Campus. These collaborations will enable the Molecular Epidemiology Laboratory to:
3. Cancer Genetics Program—MGH and BWH, Collaborative interactions
A new nodal point between the Lung Cancer Program and the Cancer Genetics Program will continue work on the molecular correlates of EGFR mutation and the response to EGFR inhibitors. The work proposed in the next five years is to further characterize mutations in EGFR in tumors and tumor cell lines from subjects with non-small-cell lung cancer. Three patient cohorts of 185 patients with previously untreated advanced non-small-cell lung cancer will be studied (#02308, #04253, and #04291); these cohorts will include those who respond to treatment, patients with stable disease, and patients with progressive non-small-cell lung cancer. Other investigation will include:
Members of the DF/HCC Lung Cancer Program and the Cancer Genetics Program have shown that point mutations, insertions, and deletions in EGFR are associated with clinical responses to the tyrosine kinase inhibitor (TKI) gefitinib in approximately 80% of patients. This finding has led to a fundamental change in treatment for some lung cancer patients.
4. Prostate Cancer (DFCI) and Biostatistics (MGH) Programs, Collaborative interactions
Collaborations begun by DF/HCC have provided investigators with access to lung cancer specimens and the ability to compare amplification findings across these different platforms. Future studies will continue to use both array CGH and single nucleotide polymorphism (SNP) arrays to identify areas of chromosomal amplification and loss and compare the mRNA expression patterns in different subsets of lung cancers, including:
An example of the application of the array CGH has been the discovery of areas of amplification on chromosome 8 associated with squamous cell carcinomas but not adenocarcinomas. The addition of expression arrays allows identification of genes that are not only amplified but also highly expressed. A complementary effort has adopted the technology of SNP arrays to identify areas of chromosomal amplification and deletion in lung cancers
5. Angiogenesis, Invasion, and Metastasis Program—TCH, Collaborative interactions
Clinical trials of VEGF inhibitors for lung cancer (bevacizumab and ZD6474) have shown life-threatening and even fatal hemoptysis following development of intraparenchymal cavities. To investigate these toxicities in more detail, a new nodal point has formed between the Angiogenesis, Invasion, and Metastasis Program and the Lung Cancer Program. This team is collaborating to investigate the effects of VEGF inhibition on lung regeneration and repair.
6. MGH, BWH, and DFCI, Collaborative interactions
Provided a mechanism to gain consent and obtain normal peripheral white blood cells on patients starting treatment