Method of treating cancer
This document provides methods and materials involved in assessing samples (e.g., cancer cells) for the presence of a loss of heterozygosity (LOH) signature. For example, methods and materials for determining whether or not a cell (e.g., a cancer cell) contains an LOH signature are provided. Materials and methods for identifying cells (e.g., cancer cells) having a deficiency in homology directed repair (HDR) as well as materials and methods for identifying cancer patients likely to respond to a particular cancer treatment regimen also are provided.
1. A method of treating cancer, comprising:
(a) predicting a cancer patient's response to a cancer treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase I inhibitor, radiation, and/or a PARP inhibitor, wherein predicting the cancer patient's response to the cancer treatment regimen comprises:
(i) determining, in the cancer cell, the total number of LOH regions in at least one pair of human chromosomes of said cancer cell that are longer than a first length but shorter than the length of the whole chromosome containing the LOH region, wherein said at least one pair of human chromosomes is not a human X/Y sex chromosome pair, wherein said first length is about 15 or more megabases, wherein the cancer cell is a breast cancer cell or an ovarian cancer cell; and
(ii) correlating said total number of LOH regions that is greater than a reference number that is at least 6 with an increased likelihood that said cancer patient will respond to said cancer treatment regimen; and
(b) based on correlating said total number of LOH regions with an increased likelihood that said cancer patient will respond to said cancer treatment regimen in (a)(ii), administering to the cancer patient a treatment regimen comprising a DNA damaging agent, an anthracycline, a topoisomerase I inhibitor, radiation, and/or a PARP inhibitor.
2. The method of claim 1 , wherein said LOH regions are determined in at least ten pairs of human chromosomes.
3. The method of claim 1 , wherein said total number of LOH Regions is 9 or more.
4. The method of claim 1 , wherein said reference number is at least 8.
5. The method of claim 1 , wherein said at least one pair of human chromosomes is not human chromosome 17.
6. The method of claim 1 , wherein said DNA damaging agent is cisplatin, carboplatin, oxalaplatin, or picoplatin, said anthracycline is epirubicin or doxorubicin, said topoisomerase I inhibitor is campothecin, topotecan, or irinotecan, or said PARP inhibitor is iniparib, olaparib or veliparib.
7. A method of treating cancer, comprising:
(a) predicting a cancer patient's response to a treatment regimen including paclitaxel or docetaxel, wherein predicting the cancer patient's response to the treatment regimen comprises:
(i) determining, in the cancer cell, the total number of LOH regions in at least one pair of human chromosomes of said cancer cell that are longer than a first length but shorter than the length of the whole chromosome containing the LOH region, wherein said at least one pair of human chromosomes is not a human X/Y sex chromosome pair, wherein said first length is about 15 or more megabases, wherein the cancer cell is a breast cancer cell or an ovarian cancer cell; and
(ii) correlating said total number that is greater than a reference number that is at least 6 with an increased likelihood that said cancer patient will not respond to the treatment regimen including paclitaxel or docetaxel, and
(b) based on correlating said total number of LOH regions with an increased likelihood that said cancer patient will not respond to said cancer treatment regimen in (a)(ii), administering to the patient a treatment regimen including a DNA damaging agent, an anthracycline, a topoisomerase I inhibitor, radiation, and/or a PARP inhibitor.
8. The method of claim 7 , wherein said LOH regions are determined in at least ten pairs of human chromosomes.
9. The method of claim 7 , wherein said total number of LOH regions LOH Regions is 9 or more.
10. The method of claim 7 , wherein said reference number is at least 8.
11. The method of claim 7 , wherein said at least one pair of human chromosomes is not human chromosome 17.