Compositions and methods of treating abnormal cell proliferation

A method of treating a subject suffering from a disorder characterized by abnormal cell-proliferation and/or cell-differentiation, comprising administering to the subject in need of such treatment a vitamin D analog and a retinoid, wherein the combination of the vitamin D analog and the retinoid is an effective combination and the retinoid and the vitamin D analog are administered simultaneously or at different times and wherein:

• (a) the vitamin D analog is capable of binding a vitamin D receptor or being converted in vivo into a compound capable of binding a vitamin D receptor;
• and
• (b) the retinoid is selected from the group consisting of retinoid D with an alcohol CH2OH terminal side chain, an ester of retinoid D having an ester bond, an ether of retinoid D having an ether bond, and retinoid D where the alcohol CH2OH terminal side chain is replaced with an aldehyde CHO terminal side chain, wherein each of the ester bond and the ether bond is formed with the oxygen at the terminal side chain of Retinoid D and wherein said retinoid D with the alcohol CH2OH terminal side chain has the structure:
• wherein the configuration at the 7-, 9-, 11- and 13-position double bonds is independently Z or E and wherein R1 is selected from the group consisting of:
• wherein the keto group at the 4-position is free or protected;
• and
• wherein X is selected from the group consisting of hydrogen and C1-6-alkyl and Y is selected from the group consisting of hydroxy and C1-6-alkyoxyl and wherein the absolute configuration at the 4-position is independently R or S.

A method of treating a subject suffering from a disorder selected from the group consisting of psoriasis, acne, atopic dermatitis, eczema, rosacea, actinic keratosis, seborrheic dermatitis, and congenital keratinization disorders, comprising administering to the subject in need of such treatment a vitamin D analog and a retinoid, wherein the combination of the vitamin D analog and the retinoid is an effective combination and the retinoid and the vitamin D analog are administered simultaneously or at different times and wherein:

• (a) the vitamin D analog is capable of binding a vitamin D receptor or being converted in vivo into a compound capable of binding a vitamin D receptor;
• and
• (b) the retinoid is selected from the group consisting of retinoid D with an alcohol CH2OH terminal side chain, an ester of retinoid D having an ester bond, an ether of retinoid D having an ether bond, and retinoid D where the alcohol CH2OH terminal side chain is replaced with an aldehyde CHO terminal side chain, wherein each of the ester bond and the ether bond is formed with the oxygen at the terminal side chain of Retinoid D and wherein said retinoid D with the alcohol CH2OH terminal side chain has the structure:
• wherein the configuration at the 7-, 9-, 11- and 13-position double bonds is independently Z or E and wherein R1 is selected from the group consisting of:
• wherein the keto group at the 4-position is free or protected;
• and
• wherein X is selected from the group consisting of hydrogen and C1-6-alkyl and Y is selected from the group consisting of hydroxy and C1-6-alkyoxyl and wherein the absolute configuration at the 4-position is independently R or S.

A method of treating one or more conditions of the skin selected from the group consisting of dry skin, photodamaged skin, age spots, aged skin, inflexibility of stratum corneum, wrinkles, fine lines, actinic blemishes, skin dyschromias, and ichthyosis, comprising applying to the skin having said one or more condition a vitamin D analog and a retinoid, wherein the combination of the vitamin D analog and the retinoid is an effective combination and the retinoid and the vitamin D analog are administered simultaneously or at different times and, wherein:

• (a) the vitamin D analog is capable of binding a vitamin D receptor or being converted in vivo into a compound capable of binding a vitamin D receptor;
• and
• (b) the retinoid is selected from the group consisting of retinoid D with an alcohol CH2OH terminal side chain, an ester of retinoid D having an ester bond, an ether of retinoid D having an ether bond, and retinoid D where the alcohol CH2OH terminal side chain is replaced with an aldehyde CHO terminal side chain, wherein each of the ester bond and the ether bond is formed with the oxygen at the terminal side chain of Retinoid D and wherein said retinoid D with the alcohol CH2OH terminal side chain has the structure:
• wherein the configuration at the 7-, 9-, 11- and 13-position double bonds is independently Z or E and wherein R1 is selected from the group consisting of:
• wherein the keto group at the 4-position is free or protected;
• and
• wherein X is selected from the group consisting of hydrogen and C1-6-alkyl and Y is selected from the group consisting of hydroxy and C1-6-alkyoxyl and wherein the absolute configuration at the 4-position is independently R or S.