COMPOSITIONS AND METHODS OF TREATING CANCER USING LIPID AGONISTS AND RECEPTORS THEREOF
Provided herein are methods for preventing or treating cancer in a subject comprising overexpressing at least one Receptor for a lipid agonist, such as G-protein receptors for Resolvin. Such methods may be combined with administering Resolvins, or lipoxins and their analogs, of said Receptors to enhance the pro-resolution effects of the Resolvins, or lipoxins and their analogs, in the local, inflammatory environment where cancer cells are already present.
1 . A method for treating oral cancer in a subject, wherein the subject comprises cells that overexpress a G-protein coupled receptor (GPCR), wherein the GPCR is selected from the group consisting of receptor for Resolvin E1 (ERV1), G protein-coupled receptor 32 (GPR32), proResolvin mediator annexin A1 (ALX/FPR2), LO-derived eicosanoid receptors LXA4 receptor (ALX), and Leukotriene B4 receptor (BLT), the method comprising:
administering at least one lipid agonist to the subject, wherein the at least one lipid agonist is selected from the group consisting of di-hydroxy members of the Resolvin E series, di-hydroxy members of the Resolvin D series, tri-hydroxy members of the Resolvin E series, tri-hydroxy members of the Resolvin D series, Resolvins derived from eicosapentaenoic acid (EPA), resolvins derived fromdocosahexaenoic acid (DHA), or endogenous lipoxins derived from arachidonic acid, lipoxins, and maresins.
2 .- 3 . (canceled)
4 . The method of claim 1 , wherein the GPCR is ERV1.
5 . The method of claim 1 , wherein the GPCR is ALX.
6 .- 12 . (canceled)
13 . The method of claim 1 , wherein the lipid agonist is a member of the Resolvin D Series.
14 . The method of claim 13 , wherein the Resolvin D Series is selected from the group consisting of Resolvin D1, D2, D3, D4, D5, and D6.
15 . The method of claim 1 , wherein the lipid agonist is a member of the Resolvin E Series.
16 . The method of claim 15 , wherein the Resolvin E Series is selected from the group consisting of Resolvin E1, E2, and E3.
17 . The method of claim 15 , wherein the Resolvin E Series is Resolvin E1.
18 . The method of claim 1 , wherein the lipid agonist is a member of the lipoxins.
19 . The method of claim 18 , wherein the lipoxins is selected from LXA4, LXB4, or analogs thereof.
20 . The method of claim 19 , wherein the lipoxin is LXA4.
21 . The method of claim 1 , wherein the lipid agonist is administered systematically.
22 . The method of claim 21 , wherein the systematic administration is selected from the group consisting of oral, intravenous, intradermal, intraperitoneal, subcutaneous, and intramuscular administration.
23 . The method of claim 21 , wherein the composition is administered intratumorally or peritumorally.
24 . The method of claim 1 , wherein the subject is treated with at least one additional anti-cancer agent, wherein the anti-cancer agent is selected from the group consisting of paclitaxel, cisplatin, topotecan, gemcitabine, bleomycin, etoposide, carboplatin, docetaxel, doxorubicin, topotecan, cyclophosphamide, trabectedin, olaparib, tamoxifen, letrozole, and bevacizumab.
25 . (canceled)
26 . The method of claim 1 , wherein the subject is treated with at least one additional anti-cancer therapy, wherein the anti-cancer therapy is radiation therapy, chemotherapy, or surgery.
27 .- 30 . (canceled)
31 . The method of claim 1 , wherein the subject is a mammal.
32 . The method of claim 31 , wherein the mammal is human.
33 . The method of claim 1 , wherein an inflammatory response is inhibited or reduced in the subject, wherein the inhibition or reduction in the inflammatory response results in a decreased expression of the NF-κB, IL-6, and IL-8 genes.
34 . (canceled)
35 . The method of claim 1 , wherein an angiogenic response is inhibited or reduced in the subject, wherein the inhibition or reduction in the angiogenic response results in a decreased expression of the Ang1, Ang2, and VEGF genes.
36 . (canceled)
37 . The method of claim 1 , wherein malignancy is inhibited or reduced in the subject.
38 . The method of claim 1 , wherein tumor necrosis is enhanced or increased in the subject.