US 2022/0065864 A1 · TEPOXALIN TARGETING OF ABCB1 OVEREXPRESSING CANCERS

Abstract

The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers that exhibit elevated expression and/or amplification of the ABCB1 (MDR1) transporter, optionally for reasons related to development of chemotherapeutic resistance having occurred during treatment with an initial chemotherapeutic drug. In particular, the instant disclosure provides for identification of a cancer as possessing elevated ABCB1 expression and/or exhibiting resistance to a non-tepoxalin chemotherapeutic drug, and selecting and/or administering tepoxalin, a tepoxalin derivative and/or metabolite thereof as a therapeutic agent for such a cancer and/or subject having or at risk of developing such a cancer. Methods and compositions for therapies that combine such tepoxalin or tepoxalin-related compounds with other cancer therapies and/or chemotherapeutic agents are also provided.

Claims22

Dependent claims

A method for selecting a treatment for a subject having or at risk of developing a cancer, the method comprising:

(a) obtaining a sample from a subject having or at risk of developing a cancer;
(b) identifying the presence or absence in the sample of one or more of the following:
high ABCB1 mRNA expression levels, high ABCB1 protein expression levels and/or amplification of the ABCB1 locus;
and
(c) selecting tepoxalin, a tepoxalin derivative or a RWJ20142 derivative as a treatment for the subject if high ABCB1 mRNA expression levels, high ABCB1 protein expression levels and/or amplification of the ABCB1 locus is observed in the sample, thereby selecting a treatment for the subject having or at risk of developing a cancer.

2 more elements

A method selected from the group consisting of:

A method for selecting a treatment for a subject having or at risk of developing a cancer selected from the group consisting of lung, colorectal, kidney, hepatic, lymphoma, bone, ovarian, biliary tract and thyroid cancer, the method comprising selecting tepoxalin, a tepoxalin derivative or a RWJ20142 derivative as a treatment for the subject, thereby selecting a treatment for the subject having or at risk of developing a cancer selected from the group consisting of lung, colorectal, kidney, hepatic, lymphoma, bone, ovarian, biliary tract and thyroid cancer;
A method for treating or preventing cancer in a subject, comprising:
(a) obtaining a sample from a subject having or at risk of developing cancer;
(b) identifying the presence or absence in the sample of one or more of the following in the sample:
high ABCB1 mRNA expression levels, high ABCB1 protein expression levels and/or amplification of the ABCB1 locus;
and
(c) administering tepoxalin, a tepoxalin derivative or a RWJ20142 derivative to the subject if one or more of high ABCB1 mRNA expression levels, high ABCB1 protein expression levels and/or amplification of the ABCB1 locus is identified in the sample,
thereby treating or preventing cancer in the subject;
A method for treating a subject having a cancer that is resistant to a non-tepoxalin chemotherapeutic drug, the method comprising administering to the subject tepoxalin, a tepoxalin derivative or a RWJ20142 derivative, thereby treating the subject having a cancer that is resistant to a non-tepoxalin chemotherapeutic drug;
and
A method for treating or preventing cancer in a subject, the method comprising co-administering to a subject having or at risk of developing cancer (i) tepoxalin, a tepoxalin derivative or a RWJ20142 derivative and (ii) a non-tepoxalin chemotherapeutic drug, thereby treating or preventing cancer in the subject.

8 more elements

Dependencies are inferred from the claim text.

Tepoxalin targeting of abcb1 overexpressing cancers

Life of this patent

Tepoxalin targeting of abcb1 overexpressing cancers

Life of this patent

Abstract

Claims22