MCT protein inhibitor-related prognostic and therapeutic methods

• US 10,085,987 B2
• Filed: 01/25/2013
• Issued: 10/02/2018
• Est. Priority Date: 01/27/2012
• Status: Active Grant

• Current Assignee: Thomas Jefferson University (Main Line Health System)
• Original Assignee: Thomas Jefferson University (Main Line Health System)
• Inventors: Lisanti, Michael P., Sotgia, Federica
• Primary Examiner(s): Hui, San Ming R
• Application Number:
  US14/374,550
• Publication Number:
  US 20140378477A1
• Time in Patent Office: 2,076 Days
• Field of Search: 5142601
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: G01N 2333/705 Assays involving receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

This invention provides a method of identifying one or more subgroups of cancer patients that are likely to benefit from treatment with a monocarboxylate transporter (MCT) protein inhibitor comprising: (a) obtaining a sample of a cancer/tumor tissue from each of said cancer patients; (b) determining the expression level of stromal MCT4 protein in each of said samples of cancer/tumor tissue to obtain a first dataset; and (c) using the expression level of the stromal MCT4 protein from said first dataset to classify each of said sets of one or more cancer patients as stromal MCT4-positive or stromal MCT4-negative, wherein the cancer patients classified as stromal MCT4-positive are patients that are more likely to benefit from treatment with said MCT protein inhibitor. This invention also provides related methods for treating a cancer/tumor whose stromal component expresses the MCT4 protein in a patient.

Claims

1. A method for treating a triple negative breast cancer/tumor whose stromal component expresses the MCT4 protein in a patient, comprising:

(a) obtaining a stromal breast tissue sample from said patient;

(b) determining the expression level of stromal MCT4 protein in said stromal breast tissue sample by staining the stromal cells for MCT4 expression;

(c) determining the expression level of stromal Cav-1 protein in said sample of cancer/tumor tissue by staining the stromal tissues for Cav-1 expression; and

(d) diagnosing the patient with a high risk cancer by scoring the stained stromal cells, said diagnosis being confirmed wherein more than 30% of said stromal cells are stained in a sample for MCT4 expression and wherein no straining of the stromal cells is identified for Cav-1 expression; and

(e) administering to said diagnosed patient with a high risk cancer, an MCT protein inhibitor wherein the MCT protein inhibitor is selected from the group consisting of AR-C15858, AR C117977, and AZD-3965, wherein AZD-3965, AR C155858 and AR C117977 are represented by the following formulas;

2. The method of claim 1, wherein the mode of administration of said compound is inhalation, oral, intravenous, sublingual, ocular, transdermal, rectal, vaginal, topical, intramuscular, intraperitoneal, epidural, subcutaneous, buccal, or nasal.