Archives of pathology & laboratory medicine
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Arch. Pathol. Lab. Med. · Oct 2012
ReviewStrategies for overcoming acquired resistance to epidermal growth factor receptor: targeted therapies in lung cancer.
Acquired resistance to targeted therapy in epidermal growth factor receptor (EGFR)-mutant lung cancer represents a valuable model for considering strategies of overcoming different types of cellular resistance mechanisms. Using existing data on resistance in EGFR-mutant lung cancer, this review will discuss 3 basic approaches for overcoming resistance to EGFR-targeted therapies: intensification of EGFR inhibition, combination of EGFR inhibitors with other targeted therapies, and changing to anticancer therapies acting via alternate pathways.
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Arch. Pathol. Lab. Med. · Oct 2012
Pathologic quantification of connective tissue disease-associated versus idiopathic usual interstitial pneumonia.
Usual interstitial pneumonia (UIP) is a common chronic interstitial pneumonitis. It can occur idiopathically (I-UIP) or in the setting of systemic connective tissue disease (CTD-UIP). Some studies suggest that CTD-UIP has a better prognosis than I-UIP. The histologic differences between CTD-UIP and I-UIP are not clearly defined. ⋯ Patients with CTD-UIP had fewer, smaller FFs than did patients with I-UIP, and patients with rheumatoid arthritis-UIP had more, larger LAs than did patients with I-UIP. Of importance, the coexistence of UIP and the nonspecific interstitial pneumonia patterns was one of the most salient features in distinguishing CTD-UIP from I-UIP because CTD-UIP demonstrated an increased prevalence of multilobar, cellular, nonspecific interstitial pneumonia patterns in areas away from the UIP fibrosis.
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Crizotinib (Xalkori), the first inhibitor of both anaplastic lymphoma kinase (ALK) and c-Met receptor kinases, has been approved in the United States, Korea, and other countries for the treatment of ALK-positive non-small cell lung cancer (NSCLC). This approval came within just 4 years of the discovery of rearrangements in the ALK gene in a subset of patients with NSCLC. Oral crizotinib 250 mg twice daily showed excellent efficacy in patients with advanced ALK-positive NSCLC, with objective response rates of 61% and 51% in ongoing phase I and II studies, respectively. ⋯ Phase III studies investigating crizotinib for the first- and second-line treatment of advanced ALK-positive NSCLC, versus current standards of care, are ongoing. Crizotinib represents a new standard of care for patients with ALK-positive NSCLC and highlights the importance of the role of the pathologist, as molecular profiling becomes a part of initial workups for newly diagnosed patients with NSCLC. This approach will ensure effective individualized treatment for patients with NSCLC.
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Arch. Pathol. Lab. Med. · Oct 2012
ReviewUpdate for pathologists on idiopathic interstitial pneumonias.
Idiopathic interstitial pneumonias are a subset of diffuse pulmonary interstitial diseases classified by international consensus in 2002 as idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia. Each is associated with a characteristic histopathologic pattern. In 2011, updated consensus guidelines were released for diagnosis and management of idiopathic pulmonary fibrosis. The entire group of idiopathic interstitial pneumonias is currently undergoing refinement, with updates expected in a forthcoming consensus classification. Many of these recent and anticipated changes are relevant to pathologists. ⋯ Diagnosis of idiopathic interstitial pneumonias by multidisciplinary discussion among clinicians, radiologists, and pathologists is now strongly encouraged. Diagnosis of idiopathic pulmonary fibrosis no longer requires surgical lung biopsy; high-resolution computed tomography is an acceptable surrogate. In the context of clinical trials, pathologists are being asked to assign levels of confidence for histologic diagnosis of usual interstitial pneumonia in patients with idiopathic pulmonary fibrosis. Acute exacerbation of idiopathic pulmonary fibrosis is now accepted and should be considered when acute lung injury is superimposed on a background of usual interstitial pneumonia. The updated classification of idiopathic interstitial pneumonias will include a separate category for rare entities, including lymphoid interstitial pneumonia and idiopathic pleuroparenchymal fibroelastosis.
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Although improvements in genomic technologies during the past decade have greatly advanced our understanding of the genomic alterations that contribute to lung cancer, and the disease has (to a degree) become a paradigm for individualized cancer treatment in solid tumors, additional challenges must be addressed before the goal of personalized cancer therapy can become a reality for lung cancer patients.