Abstract: In one aspect, provided herein are methods for treating colorectal cancer in a human subject, the methods comprising administering to the human subject a composition comprising a mitogen-activated protein kinase kinase (MEK) inhibitor and a composition comprising bisphosphonate. In a particular aspect, provided herein is a method for treating colorectal cancer in a human subject, the method comprising administering to the human subject trametinib dimethyl sulfide or a composition thereof and zoledronic acid or a composition thereof.

Abstract: The invention relates to improved methods for treating a human subject diagnosed with cancer using combination drug regimens tailored to the genome/proteome/phenome of the subject's turn or/cancer. The treatment regimens are selected and/or their efficacy is confirmed using an animal model “avatar,” preferably a transgenic Drosophila avatar, of the genome/proteome/phenome of the subject. In certain embodiments, “avatar armies” representing the genomes/proteomes/phenomes of a population of patients diagnosed with a disease or disorder can be used to screen and select therapeutic regimens for treatment and/or to screen for new lead compounds and identify new therapeutics for the disease or disorder.

Abstract: The present invention provides a method for treating a subject afflicted with a cancer which comprises administering to the subject (i) a proteasome antagonist and (ii) a PI3K signal transduction pathway antagonist, each of (i) and (ii) in an amount such that when both (i) and (ii) are administered, the administration is effective to treat the subject. The present invention also provides a method for treating a subject afflicted with a cancer which comprises administering to the subject (i) a proteasome antagonist, and (ii) an oligonucleotide which decreases the amount of PI3K, mTor, TORC1, TORC2, AKT, or JNK produced by cells of the cancer. The present invention provides processes for identifying whether a compound is an epithelial cancer drug candidate. The present invention also provides a method for identifying a cancer patient who will likely benefit from treatment with a PI3K signal transduction pathway antagonist.

Abstract: High throughput methods for screening of anti-cancer compounds using Drosophila are described. The methods involve modifying the expression of dCsk and observing the effect of putative anti-cancer candidate compounds on resulting expressed characteristics in the Drosophila. Related animal models and apparatus are also provided.

Abstract: High throughput drug screening assay methods and related apparatus are described. Drosophila with screenably distinct characteristics are raised in multi-well microtiter plates on standard growth medium. Screenably distinct characteristics which mimic human cancer or cancer-related condition are established by modifying expression of an oncogene or tumor suppressor in the Drosophila. Compounds that putatively modify the screenably distinct characteristic are then tested by feeding the compounds to the Drosophila embryos, and determining whether the compound modifies the screenably distinct characteristic induced by modifying gene expression. The assay methods and related articles of composition can also be used to simultaneously assay toxicity of candidate compounds.

Abstract: High throughput drug screening assay methods and related apparatus are described. Wild-type Drosophila are raised in multi-well microtiter plates on a growth medium having a high level of a sugar such as glucose. The high sugar diet during development induces screenably distinct characteristics in the wild-type Drosophila. Compounds that putatively modify the screenably distinct characteristic are tested by feeding to the Drosophila embryos, and determining whether the compound modifies the screenably distinct characteristic induced by the high sugar growth medium. The assay methods and related articles of composition can also be used to assay toxicity of candidate compounds.