Treatments of therapy resistant diseases and drug combinations for treating the same
First Claim
1. A drug combination for use in therapy-resistant breast cancer comprising a PI3K pathway inhibitor, an estrogen receptor (ER) antagonist, and an HDAC inhibitor or a pharmaceutically acceptable salt thereof.
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Abstract
The present invention provides novel methods and kits for diagnosing the presence of cancer within a patient, and for determining whether a subject who has cancer is susceptible to different types of treatment regimens. The cancers to be tested include, but are not limited to, prostate, breast, lung, gastric, ovarian, bladder, lymphoma, mesothelioma, medullablastoma, glioma, and AML. Identification of therapy-resistant patients early in their treatment regimen can lead to a change in therapy in order to achieve a more successful outcome. One embodiment of the present invention is directed to a method for diagnosing cancer or predicting cancer-therapy outcome by detecting the expression levels of multiple markers in the same cell at the same time, and scoring their expression as being above a certain threshold, wherein the markers are from a particular pathway related to cancer, with the score being indicative or a cancer diagnosis or a prognosis for cancer-therapy failure. This method can be used to diagnose cancer or predict cancer-therapy outcomes for a variety of cancers. The markers can come from any pathway involved in the regulation of cancer, including specifically the PcG pathway and the “stemness” pathway. The markers can be mRNA, microRNA, DNA, or protein.
51 Citations
26 Claims
- 1. A drug combination for use in therapy-resistant breast cancer comprising a PI3K pathway inhibitor, an estrogen receptor (ER) antagonist, and an HDAC inhibitor or a pharmaceutically acceptable salt thereof.
- 10. A drug combination for use in therapy-resistant prostate cancer comprising a PI3K pathway inhibitor, an estrogen receptor (ER) antagonist, and an mTOR inhibitor or a pharmaceutically acceptable salt thereof.
- 19. A drug combination for use in therapy-resistant ovarian or lung cancer comprising two or more compounds selected from the group consisting of a PI3K Inhibitor, an ER antagonist, a PKC inhibitor, an AMP kinase activator, a selective ER modulator, and an anti-epileptic drug, or a pharmaceutically acceptable salt thereof.
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23. A method of computationally designing a combination of drugs to administer to a patient in need thereof, the method comprising the following steps:
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a) identifying cancer therapy outcome predictor (CTOP) signatures, wherein the CTOP signatures are gene expression signatures discriminating patients with therapy-resistant versus therapy-responsive phenotypes; b) calculating the CTOP score for each individual CTOP signature for the patient, using weighted scoring algorithm; c) calculating for the patient cumulative CTOP scores representing a sum of individual CTOP scores; d) classifying the patient into a group with a distinct likelihood of therapy failure based on the values of cumulative CTOP scores, wherein patients with higher numerical values of CTOP scores are more likely to fail existing cancer therapies and patients with lower numerical values of CTOP scores are less likely to fail the existing cancer therapies; e) defining the individual CTOP profile for the patient, comprising a set of values of individual CTOP scores; f) using the connectivity map (CMAP) database to identify individual drugs inhibiting and/or activating the expression of genes comprising CTOP signatures; and g) selecting the drugs targeting multiple CTOP signatures at the drug'"'"'s lowest concentration;
thereby designing drug combinations by using individual drugs which most efficiently target CTOP signatures. - View Dependent Claims (24, 25, 26)
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Specification