A T Shaw

Publications (2)6.43 Total impact

• Article: Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice.

  L V Sequist, R S Heist, A T Shaw, P Fidias, R Rosovsky, J S Temel, I T Lennes, S Digumarthy, B A Waltman, E Bast, [......], N C Choi, J Baselga, T J Lynch, L W Ellisen, M Mino-Kenudson, M Lanuti, D R Borger, A J Iafrate, J A Engelman, D Dias-Santagata
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  ABSTRACT: Personalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is becoming essential to optimal cancer care. We developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping. Pathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had ≥1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and β-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy. Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice.
  Annals of Oncology 11/2011; 22(12):2616-24. · 6.43 Impact Factor
• Article: Mouse models of human non-small-cell lung cancer: raising the bar.

  C F B Kim, E L Jackson, D G Kirsch, J Grimm, A T Shaw, K Lane, J Kissil, K P Olive, A Sweet-Cordero, R Weissleder, T Jacks
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  ABSTRACT: Lung cancer is a devastating disease that presents a challenge to basic research to provide new steps toward therapeutic advances. The cell-type-specific responses to oncogenic mutations that initiate and regulate lung cancer remain poorly defined. A better understanding of the relevant signaling pathways and mechanisms that control therapeutic outcome could also provide new insight. Improved conditional mouse models are now available as tools to improve the understanding of the cellular and molecular origins of adenocarcinoma. These models have already proven their utility in proof-of-principle experiments with new technologies including genomics and imaging. Integrated thinking to apply technological advances while using the appropriate mouse model is likely to facilitate discoveries that will significantly improve lung cancer detection and intervention.
  Cold Spring Harbor Symposia on Quantitative Biology 02/2005; 70:241-50.