Methods of treating head and neck cancer
View Patent ↗Methods of treating a head and neck cancer are disclosed.
1. A method of treating a subject having a squamous cell carcinoma of the head and neck (HNSCC), the method comprising:
acquiring knowledge that the subject has a mutation in a cell-cycle gene; and
administering to the subject a cyclin dependent kinase (CDK) inhibitor that inhibits one or both of cyclin dependent kinase 4 (CDK4) or cyclin dependent kinase 6(CDK6),
thereby treating the HNSCC in the subject.
2. The method of claim 1 , wherein the cell-cycle gene is chosen from a cyclin dependent kinase inhibitor 2A (CDKN2A) gene, a cyclin dependent kinase inhibitor 2B (CDKN2B) gene, a Cyclin E1(CCNE1) gene, a Cyclin D1(CCND1) gene, a Cyclin D2 (CCND2) gene, a Cyclin D3 (CCND3) gene, a CDK4 gene, a CDK6 gene, or a gene described in Table 1 or Table 4.
3. The method of claim 1 , wherein the subject has one or more of:
(i) a loss-of-function mutation in a CDKN2A gene;
(ii) a gain-of-function mutation in a CCND1 gene;
(iii) a mutation or a mutant polypeptide described in Table 1 or 4; or
(iv) a mutant CDKN2A, CDKN2B, or CCND1 polypeptide.
4. The method of claim 1 , wherein the mutation in the cell-cycle gene is detected in a nucleic acid molecule by one or more of: sequencing, a nucleic acid hybridization assay, an amplification-based assay, a PCR-RFLP assay, real-time PCR, screening analysis, FISH, spectral karyotyping, MFISH, comparative genomic hybridization, in situ hybridization, SSP, HPLC, or mass-spectrometric genotyping.
5. The method of claim 1 , wherein the knowledge that the subject has a mutation in a cell-cycle gene is obtained from a sample isolated from the subject, wherein the sample is a blood sample, a serum sample, a urine sample, a tissue sample, or a buccal swab, or comprises a cell from a tumor biopsy or a circulating tumor cell.
6. The method of claim 5 , wherein the sample is positive for CCND1 by immunohistochemistry.
7. The method of claim 1 , wherein the CDK inhibitor inhibits both CDK4 and CDK6.
8. The method of claim 1 , wherein the CDK inhibitor is chosen from LEE011, LY-2835219, or PD 0332991.
9. The method of claim 8 , wherein the CDK inhibitor is LEE011.
10. The method of claim 8 , wherein the CDK inhibitor is LY-2835219.
11. The method of claim 8 , wherein the CDK inhibitor is PD 0332991.
12. The method of claim 1 , further comprising administering a radiation therapy to the subject, performing a surgery on the subject, or both.
13. The method of claim 1 , wherein the HNSCC is localized.
14. The method of claim 1 , wherein the subject has metastatic cancer.
15. A method of treating a subject having an HNSCC, the method comprising:
selecting a subject having a mutation in a cell-cycle gene; and
administering to the selected subject a CDK inhibitor chosen from LEE011,LY-2835219, PD 0332991, Indisulam, AZD5438, SNS-032, SCH 727965, JNJ-7706621, indirubin, or Seliciclib,
thereby treating the HNSCC in the subject.
16. The method of claim 15 further comprising acquiring knowledge of whether the subject has a mutation in a cell-cycle gene.
17. The method of claim 15 , wherein the cell-cycle gene is chosen from a cyclin dependent kinase inhibitor 2A (CDKN2A) gene, a cyclin dependent kinase inhibitor 2B (CDKN2B) gene, a Cyclin E1 (CCNE1) gene, a Cyclin D1 (CCND1) gene, a Cyclin D2 (CCND2) gene, a Cyclin D3 (CCND3) gene, a cyclin dependent kinase 4 (CDK4) gene, a cyclin dependent kinase 6 (CDK6) gene, or a gene described in Table 1 or Table 4.
18. The method of claim 15 , wherein said mutation is chosen from:
(i) a loss-of-function mutation in a CDKN2A gene;
(ii) a gain-of-function mutation in a CCND1 gene;
(iii) a mutation or a mutant polypeptide described in Table 1 or 4; or
(iv) a mutant CDKN2A, CDKN2B or CCND1 polypeptide.
19. The method of claim 15 , wherein the CDK inhibitor is chosen from LEE011, LY-2835219, or PD 0332991.
20. A method for generating a personalized cancer treatment report, the method comprising:
acquiring a sample from a subject having an HNSCC;
determining whether the subject has a mutation in a cell-cycle gene;
selecting a CDK inhibitor that inhibits one or both of CDK4 or CDK6 as a treatment, if the subject has a mutation in a cell-cycle gene; and
generating a personalized cancer treatment report to memorialize the presence or absence of a mutation in a cell cycle gene in the subject.
21. The method of claim 20 , wherein the cancer treatment report comprises one or more of the following:
(i) information on prognosis, resistance, or potential therapeutic options;
(ii) information on the likely effectiveness of a therapeutic option;
(iii) the acceptability of a therapeutic option, or the advisability of applying the therapeutic option to the subject; or
(iv) information on the administration of a drug.
22. The method of claim 20 , wherein the CDK inhibitor is chosen from LEE011, LY-2835219, or PD 0332991.