Faculty Bibliography

The management of advanced non-small cell lung cancer (NSCLC) has been revolutionized in recent years with the introduction of biomarker-targeted molecular therapies and immune checkpoint inhibitors. In contrast, since adjuvant chemotherapy was first established twenty years ago as the standard of care, little has changed for resected early-stage (IB-IIIA) patients for whom the potential for cure is greatest. In this manuscript we will review recently presented data as well as ongoing/planned studies in this arena. So far, investigative efforts have yielded mixed results regarding the use of tyrosine kinase inhibitors (TKIs) in early-stage NSCLC, though a series of now better planned, biomarker-driven ongoing phase III trials may be more informative. Several innovative immunotherapy studies have already shown promising results principally in the neoadjuvant setting with a large number of pivotal neo-adjuvant and adjuvant trials now in progress. Given the more robust design and biomarker-focused approach of the new generation of studies, significant advances in the optimal curative treatment of early stage NSCLC are anticipated.

Thyroid cancer incidence and diagnostic radiography exposures, particularly computed tomography (CT) scanning and nuclear medicine examinations, have increased substantially in the USA. However, very few epidemiologic studies have directly investigated their associations. A population-based case-control study was conducted in Connecticut in 2010-2011, including 462 histologically confirmed incident thyroid cancer cases and 498 population-based controls. Multivariate unconditional logistic regression models were used to estimate the associations between diagnostic radiography and the risk of thyroid cancer, controlling for potential confounding factors. Exposure to any form of diagnostic radiography was associated with an increased risk of well-differentiated thyroid microcarcinoma [tumor size≤10 mm, odds ratio (OR)=2.76, 95% confidence interval (CI): 1.31-5.81]. The highest risk increase occurred with nuclear medicine examinations (excluding cardiology tests and thyroid uptake studies; OR=5.47, 95% CI: 2.10-14.23), followed by chest CT scanning (OR=4.30, 95% CI: 1.66-11.14), head and neck CT scanning (OR=3.88, 95% CI: 1.75-8.63), upper gastrointestinal series (OR=3.56, 95% CI: 1.54-8.21), lower gastrointestinal series (OR=3.29, 95% CI: 1.41-7.66), kidney radiography involving dye injection into a vein or artery (OR=3.21, 95% CI: 1.20-8.54), mammography (OR=2.95, 95% CI: 1.14-7.61), chest radiography (OR=2.93, 95% CI: 1.37-6.29), and abdomen CT scanning (OR=2.54, 95% CI: 1.02-6.30). No significant associations were found between these imaging modalities and thyroid tumors larger than 10 mm. This study provides the first direct evidence that CT scanning and nuclear medicine examinations are associated with an increased risk of thyroid cancer. The novel finding that an array of diagnostic radiography procedures are associated with thyroid microcarcinomas warrants further investigation.

Methods for rapid surface immobilization of bioactive small molecules with control over orientation and immobilization density are highly desirable for biosensor and microarray applications. In this Study, we use a highly efficient covalent bioorthogonal [4+2] cycloaddition reaction between trans-cyclooctene (TCO) and 1,2,4,5-tetrazine (Tz) to enable the microfluidic immobilization of TCO/Tz-derivatized molecules. We monitor the process in real-time under continuous flow conditions using surface plasmon resonance (SPR). To enable reversible immobilization and extend the experimental range of the sensor surface, we combine a non-covalent antigen-antibody capture component with the cycloaddition reaction. By alternately presenting TCO or Tz moieties to the sensor surface, multiple capture-cycloaddition processes are now possible on one sensor surface for on-chip assembly and interaction studies of a variety of multi-component structures. We illustrate this method with two different immobilization experiments on a biosensor chip; a small molecule, AP1497 that binds FK506-binding protein 12 (FKBP12); and the same small molecule as part of an immobilized and in situ-functionalized nanoparticle.