Patients with non-small cell lung cancer (NSCLC) that has spread to other parts of the body.

Inclusion Criteria:

1. Patient diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration
2. Patient diagnosis of either stage IIIB, stage IV, or advanced, incurable NSCLC, & failed at least one front-line metastatic NSCLC chemotherapy regimen. (Patients who failed adjuvant or locally advanced therapy within 6 months are also eligible to participate in study).
3. Patient has uni-dimensionally measurable NSCLC.
4. Karnofsky performance status >/= 60 or ECOG performance status 0-2
5. Patient has biopsy accessible tumor.

6. Patient has adequate hematologic function as defined by absolute neutrophil count (ANC) >/= 1,500/mm^3, platelet count >/= 100,000/mm^3, WBC

   • 3,000/ mm^3, and hemoglobin >/= 9 g/dL.
7. Patient has adequate hepatic function as defined by total bilirubin level </= 1.5 X upper limit of normal, & alkaline phosphatase, AST or ALT </= 2.5 X upper limit of normal.
8. Patient has adequate renal function as defined by serum creatinine level </= 1.5 mg/dL or calculated creatinine clearance of >/= 60cc/minute.
9. Patient has PT < 1.5 x upper limit of normal
10. If patient has brain metastasis, must have been stable (treated or asymptomatic) for min. 4 weeks after radiation if treated w/radiation & not used steroids for at least 1 week. Re-imaging performed after 2 weeks, upon completion of radiation therapy.
11. Patient >/= 18 years of age.
12. Patient signed informed consent.
13. Patient eligible if disease free from previously treated malignancy, other than previous NSCLC, for > two years. Patients w/history of prior basal cell carcinoma of skin or pre-invasive carcinoma of cervix are exempt from exclusion.
14. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry & for duration of study participation. Childbearing potential defined as women who have had menses w/in past 12 months, not had tubal ligation or bilateral oophorectomy.Should a woman become pregnant or suspect she is pregnant while participating in study,she should inform her treating physician immediately. The patient,if a man,agrees to use effective contraception or abstinence.
15. Subject must be considered legally capable of providing his/her own consent for participation in study.

Exclusion Criteria:

1. Patient received prior investigational therapy, chemotherapy, surgery, or radiotherapy w/in 4 weeks of initiating study drug
2. Patient has undergone prior thoracic or abdominal surgery w/in 28 days of study entry, excluding prior diagnostic biopsy.
3. Patient received radiation therapy to measurable tumor w/in 6 months. Patients are allowed local irradiation for management of tumor-related symptoms (bones, brain). However, if patient has active new disease growing in previously irradiated site, patient eligible to participate in study.
4. Patient has significant medical history or unstable medical condition (unstable systemic disease: congestive heart failure (NY Heart Association Functional Classification class II or worse), recent myocardial infarction w/in 3 months, unstable angina, active infection (i.e. currently treated with antibiotics), uncontrolled hypertension). Patients w/controlled diabetes allowed. Patient must be able to undergo procedure for tissue acquisition.
5. Patient has uncontrolled seizure disorder, active neurologic disease, or neuropathy >/= grade 2. Patients w/meningeal or CNS involvement by tumor are eligible for study if above exclusion criteria are not met.
6. Patient is pregnant (confirmed by serum Beta-HCG if applicable) or is breastfeeding.
7. Any condition that's unstable or could jeopardize safety of patient & compliance in study, in investigator's judgment.
8. Patient's actively taking herbal remedies or over the counter biologics (e.g., shark cartilage, high dose antioxidants).
9. Patients allowed prior biologic (i.e. VEGF, EGFR, etc.) therapy. However, excluded from a given study if he/she has received same therapy as clinical trial (i.e. If patient previously treated w/bevacizumab, they are allowed to enroll in any of 4 studies. If patient has been previously treated w/erlotinib, they are excluded from clinical trials w/erlotinib). In addition, if patient previously treated w/gefitinib (Iressa), they are excluded from clinical trials w/erlotinib.