The purpose of this study is to try to learn more about how small molecule kinase inhibitor medications work in treating lung cancer. Crizotinib (PF-02341066) is a drug that has been shown to shrink tumors in some patients with lung cancer. While the investigators know how this drug works to stop the growth of tumors that depend on change in the gene named ALK (also called EML4-ALK), the investigators do not know why the drug stops working. The investigators would like to examine the tumor to help us better understand why crizotinib has stopped working as well as it once did. The tumor will be examined with multiple tests to look for the reason that crizotinib stopped working.

Inclusion Criteria:

• ≥18 years of age
• Histologically proven diagnosis of NSCLC at MSKCC Tumor positive for a translocation or inversion event involving the ALK gene locus
• Clinical response to treatment with crizotinib as defined by either:

Radiographic partial or complete response defined by RECIST or WHO

OR:

Radiographic stable disease for at least 8 weeks

• Radiographic progression of disease amenable to biopsy while on treatment with crizotinib as defined by RECIST or WHO
• Signed informed consent

Exclusion Criteria:

• Deemed by their treating physician to be medically unfit for biopsy
• Women who are pregnant or breast-feeding

All patients seen by the Thoracic Oncology Service who have been diagnosed with an ALK mutant NSCLC and treated with an ALK kinase inhibitor who have experienced objective regression by RECIST, WHO, or clinical criteria and who then progress will be screened for this protocol.