The invention provides biomarkers and combinations of biomarkers useful in diagnosing lung diseases such as non-small cell lung cancer or reactive airway disease. The invention also provides methods of differentiating lung disease, methods of monitoring therapy, and methods of predicting a subject's response to therapeutic intervention based on the extent of expression of the biomarkers and combinations of biomarkers. Kits comprising agents for detecting the biomarkers and combination of biomarkers are also provided.

A compound represented by the following general formula (I) [the symbol in the formula are as defined in the description], a salt thereof, or the like is a RET inhibitor or RET tyrosine kinase inhibitor that can he used as an agent for the prevention or treatment of disorders including cancers and cancer metastasis having mutations in RET. ##STR00001##

This disclosure provides reagents and methods of predicting the responsiveness of a patient to NaPi2b-targeted antibody-drug conjugates (e.g., NaPi2b-targeted antibody-polymer-drug conjugates).

Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.

Methods and compositions are provided for diagnosing lung cancer in a mammalian subject by use of 10 or more selected genes, e.g., a gene expression profile, from the blood of the subject which is characteristic of disease. The gene expression profile includes 10 or more genes of Table I or Table II herein.

Disclosed herein are biomarkers associated with a disease state such as lung cancer, and methods of discovering or using biomarkers. Also disclosed herein are classifiers built on biomarkers and methods of detecting the disease state in samples from subjects. The method may include obtaining a data set that includes protein information from a biofluid sample, and may involve using a classifier to identify the sample as indicative of a healthy state, a disease state, or a comorbidity.

A biomarker panel for a urine test for detecting lung cancer detects a biomarker selected from the group of biomarkers consisting of DMA, C5:1, C10:1, ADMA, C5-OH, SDMA, and kynurenine, or a combination thereof. A biomarker panel for a serum test for detecting lung cancer detects a biomarker selected from the group of biomarkers consisting of valine, arginine, ornithine, methionine, spermidine, spermine, diacetylspermine, C10:2, PC aa C32:2, PC ae C36:0, and PC ae C44:5; and lysoPC a C18:2, or a combination thereof.

The present invention is based on the identification of novel biomarkers predictive of responsiveness to anti-immune checkpoint inhibitor therapies.

A method of providing a treatment to a patient having non-small cell lung cancer is provided comprising extracting total RNA from a formalin fixed and paraffin embedded tumor of non-small cell lung cancer of a patient after the surgical resection, generating complementary DNA (cDNA) of the extracted total RNA from the patient's tumor, quantifying of mRNA expression of 7 genes of ABCC4 (SEQ ID NO:1), CCL19 (SEQ ID NO:2), SLC39A8 (SEQ ID NO:3), CD27 (SEQ ID NO:4), FUT7 (SEQ ID NO:5), ZNF71 (SEQ ID NO:6), and DAG1 (SEQ ID NO:7), normalizing of the quantification of the 7 genes with the quantification of a control gene UBC (SEQ ID NO:8) or a housekeeping gene, and utilizing the normalized 7 gene mRNA expression quantification to determine whether the patient will benefit from receiving adjuvant chemotherapy or not.

This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1 (PD-L1), Serine/Threonine Kinase 11 (STK11), or both PD-L1 and STK11.