Methods and materials for assessing and treating cancer

Patent metadata

Field	Value
Publication number	US-2023201192-A1
Application number	US-202117928503-A
Country	US
Kind code	A1
Filing date	Jun 16, 2021
Priority date	Jun 19, 2020
Publication date	Jun 29, 2023
Grant date	—

Abstract

This document relates to methods and materials involved in assessing and/or treating mammals (e.g., humans) having cancer (e.g., a SCD1-associated cancer). For example, methods for determining whether or not a cancer is likely to be responsive to one or more stearoyl CoA desaturase 1 (SCD1) polypeptide inhibitors (e.g., a selective SCD1 inhibitor (SSI)) are provided. In some cases, the methods and materials for treating a mammal by administering, to the mammal, one or more cancer treatments that is/are selected based, at least in part, on whether or not the mammal is likely to be responsive to one or more SCD1 polypeptide inhibitors e.g., SSI-4) are provided.

First claim

1 - 17 . (canceled)

18 . A method for treating a mammal having a SCD1-associated cancer, wherein said method comprises:
(a) detecting a decreased level of p-Src polypeptide expression in a sample obtained from said mammal; and (b) administering a SCD1 polypeptide inhibitor to said mammal.

19 . A method for treating a SCD1-associated cancer, wherein said method comprises administering a SCD1 polypeptide inhibitor to a mammal identified as having a decreased level of p-Src polypeptide expression in a sample obtained from said mammal.

20 . The method of claim 18 , wherein said mammal is a human.

21 . The method of claim 18 , wherein said sample comprises cancer cells of said cancer.

22 . The method of claim 18 , wherein said cancer is a solid tumor, and wherein said cancer is selected from the group consisting of a liver cancer, a renal cell carcinoma, an ovarian cancer, a breast cancer, a prostate cancer, a colon cancer, a pancreatic cancer, a bladder cancer, a lung cancer, a thyroid cancer, a melanoma, a brain cancer, a stomach cancer, a cervical cancer, a uterine cancer, a chronic lymphocytic leukemia, a, acute lymphocytic leukemia, and a lymphoma.

23 . The method of claim 22 , wherein said cancer is a liver cancer.

24 . The method of claim 23 , wherein said liver cancer is a hepatocellular carcinoma.

25 . The method of claim 23 , wherein said liver cancer is a cholangiocarcinoma.

26 . The method of claim 18 , further comprising detecting an elevated level of c-Myc polypeptide expression in a sample from said mammal.

27 . The method of claim 18 , further comprising detecting an elevated level of LDHA polypeptide expression in a sample from said mammal.

28 - 30 . (canceled)

31 . The method of claim 18 , wherein said SCD1 polypeptide inhibitor is a compound having Formula (II) or Formula (IIa):

or a pharmaceutically acceptable salt thereof;
wherein:
R 1 is halo;
X is —(C═O)NR 4 —;
Y is

and
R 2 , R 3 , and R 4 are each independently H or an unsubstituted C 1-6 alkyl.

32 . The method of claim 31 , wherein said SCD1 polypeptide inhibitor is SSI-4, 2-{[4-(2-Chlorophenoxy)piperidine-1-carbonyl]amino}-N-methylpyridine-4-carboxamide:

or a pharmaceutically acceptable salt thereof.

33 . The method of claim 18 , wherein said SCD1 polypeptide inhibitor is a compound having Formula (I) or Formula (Ia):

or a pharmaceutically acceptable salt thereof;
wherein:
R 1 is an unsubstituted C 1-6 alkyl or C 1-6 haloalkyl;
X is

Y is selected from:

m is 0 or 1;
n is 0, 1, or 2;
V is NR 4 or O;
R 2 , R 3 , and R 4 are each independently H or an unsubstituted C 1-6 alkyl; and
Z is an unsubstituted aryl.

34 . The method of claim 33 , wherein said SCD1 polypeptide inhibitor is SSI-2,2-(benzyloxy)-5-{[hydroxy({4-[2-(trifluoromethyl)benzoyl]piperazin-1-yl})methyl]amino}-1,2-dihydropyridin-2-ylium-1-ide:

or a pharmaceutically acceptable salt thereof.

35 . The method of claim 18 , wherein said method further comprises administering a cancer treatment to said mammal.

36 . The method of claim 35 , wherein said cancer treatment comprises a kinase inhibitor.

37 . The method of claim 36 , wherein said kinase inhibitor is regorafenib.

38 . The method of claim 35 , wherein said cancer treatment comprises a mTOR inhibitor.

39 . The method claim 35 wherein said cancer treatment comprises a proteosome inhibitor.

40 . The method of claim 35 , wherein said cancer treatment comprises an immune checkpoint inhibitor.

Assignees

• Mayo Found Medical Education & Res

Inventors

• Copland Iii John A
• Marlow Laura Ann

Classifications

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title