Fluorocyclopentenylcytosine methods of use
The disclosed subject matter provides methods using and kits comprising a compound of formula (I) or a hydrate, a solvate, or a pharmaceutically acceptable salt thereof. The disclosed subject matter further provides a method of treating one or more symptoms of cancer comprising administering to a subject in need thereof a compound of formula (I) and a process for preparing such.
1. A method of treating a human subject in need thereof with a compound of formula (I)
or a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, comprising the steps of:
collecting a sample of tumor cell or tissue from the subject;
(ii) measuring the level of UCK2 expression in the tumor cell or tissue; and
(iii) administering to the subject the compound of formula (I) at a dosage of about 300-1,000 mg/day, if an increased expression of UCK2 is measured in the tumor cell or tissue.
2. The method of claim 1 , wherein the increased expression level is determined when the amount of UCK2 expression is greater than a predetermined level of UCK2 in a non-tumor cell.
3. The method of claim 2 , wherein the non-tumor cell is a non-tumor cell of the subject.
4. The method of claim 1 , wherein the increase in the expression level is by 5% or more.
5. The method of claim 1 , wherein the tumor cell is ovarian cancer; metastatic breast cancer; adenocarcinoma of the pancreas; gastrointestinal cancer such as colorectal adenocarcinoma or cancer of the esophagus, stomach, pancreas, small bowel, hepatobiliary tract, colon, rectum or anus; bladder cancer such as metastatic bladder cancer, muscle invasive bladder cancer or non-muscle invasive bladder cancer; cervical cancer; lung cancer; non-small cell lung cancer; or renal cell carcinoma.
6. The method of claim 1 , wherein the tumor cell is a lung cancer cell.
7. The method of claim 1 , wherein the tumor cell is a non-small cell lung cancer cell.
8. A method of treating a human subject in need thereof with a compound of formula (I)
or a hydrate, a solvate, or a pharmaceutically acceptable salt thereof, comprising the steps of:
(i) collecting a sample of tumor cell or tissue from the subject;
(ii) measuring one of a protein kinase or p53 expression level in the sample;
(iii) contacting the tumor cell or tissue with a compound of formula (I);
(iv) measuring one of protein kinase or p53 expression level in the tumor cell or tissue after said contacting with the compound of formula (I); and
(v) administering to the subject the compound of formula (I) at a dosage of about 300-1,000 mg/day, if an increase in protein kinase or p53 expression level is detected.
9. The method of claim 8 , wherein said contacting the tumor cell or tissue with a compound of formula (I) by comprises administering the compound of formula (I) to the subject.
10. The method of claim 8 , wherein said measuring protein kinase or p53 expression level in the tumor cell or tissue after contacting with the compound of formula (I) comprises collecting a second sample of tumor cell or tissue from the subject and measuring one of a protein kinase or p53 expression level in the second sample.
11. The method of claim 8 , wherein the increase of protein kinase or p53 expression is by 5% or more.
12. The method of claim 8 , further comprising the step of measuring protein Cdc25C or p-Cdc25C expression level in steps (ii) and (iv), wherein a decrease in protein Cdc25C or p-Cdc25C expression level indicates likelihood of efficacy.
13. The method of claim 12 , wherein the decrease in protein Cdc25C or p-Cdc25C expression level is by 5% or more.
14. The method of claim 12 , wherein the subject is administered the compound of formula (I) if the increase in protein kinase or p53 expression level and a decrease in the protein Cdc25C or p-Cdc25C expression level are detected.
15. The method of claim 8 , wherein the protein kinase or p53 expression level is an expression level of a checkpoint kinase.
16. The method of claim 15 , wherein the checkpoint kinase is Chk1 or Chk2.
17. The method of claim 8 , wherein the protein kinase or p53 expression level is an expression level of p53.