METHODS AND COMPOSITIONS FOR PREDICTING RESISTANCE TO ANTICANCER TREATMENT

摘要

The instant application provides methods and related compositions pertaining to the identification of resistance to anticancer treatment in a patient. In a particular embodiment, the invention provides biomarkers for the identification of resistance to anticancer treatment in a lung cancer patient, wherein a reduced expression of a MEDIATOR and/or SW1/SNF complex gene in the lung cancer cells of the patient indicates that the lung cancer cells in the patient may be resistant to treatment with a receptor tyrosine kinase inhibitor, such as gefitinib and/or erlotinib. In some embodiments, the invention relates to methods and related compositions for predicting resistance to anticancer treatment by detecting the expression levels of one or more TGF-beta pathway nucleic acids and/or proteins.

主权项

1. A method of predicting resistance to anticancer treatment in a patient in need thereof, comprising:
(a) measuring expression levels of one or more SWI/SNF complex nucleic acid and/or proteins in the patient; and (b) comparing the expression levels of the one or more SWI/SNF complex nucleic acid and/or proteins in (a) with the expression levels of one or more reference SWI/SNF complex nucleic acid and/or proteins, wherein the one or more reference SWI/SNF complex nucleic acid and/or proteins are from a control sample,wherein a reduction in the expression of the one or more SWI/SNF complex nucleic acid and/or proteins in comparison to the one or more reference SWI/SNF complex nucleic acid and/or proteins is indicative of resistance to anticancer treatment in the patient; and/or
(c) isolating nucleic acid from the patient, wherein the nucleic acid comprises one or more SWI/SNF complex DNA and/or RNA; and (d) analyzing the nucleic acid of (c) for the presence of one or more inactivating mutations in the SWI/SNF complex DNA and/or RNA in comparison to one or more reference SWI/SNF complex DNA and/or RNA,wherein the presence of one or more inactivating mutations in the one or more SWI/SNF complex DNA and/or RNA analyzed in (d) is indicative of resistance to anticancer treatment in the patient; and/or
(e) isolating protein from the patient, wherein the protein comprises one or more SWI/SNF complex proteins; (f) analyzing the activity of the one or more SWI/SNF complex proteins in (e); and (g) comparing the activity of the one or more SWI/SNF complex proteins in (f) with the activity of one or more reference SWI/SNF complex proteins,wherein a difference in activity of the one or more SWI/SNF complex proteins from (f) in comparison to the one or more SWI/SNF complex reference proteins in (g) is indicative of resistance to anticancer treatment in the patient.