Compositions and methods for the treatment of cancer
Disclosed herein are methods and compositions for the treatment of cancer. In particular, the present invention discloses inhibitors of the Fanconi anemia pathway and methods using same. Such inhibitors are useful in inhibiting DNA damage repair and can be useful, for example, in the treatment of cancer.
1. A method comprising:
(a) providing a subject sample from a subject with a neoplastic disorder wherein said subject sample has been exposed to a genotoxic anti-neoplastic agent;
(b) determining the number of FANC D2-containing foci in said subject sample; and
(c) comparing the number in (b) with the number of FANC D2-containing foci in a normal tissue sample that has been exposed to said genotoxic anti-neoplastic agent.
2. The method of claim 1 , wherein the number of FANC D2-contaning foci is determined using an antibody specific for monoubiquitinated FANC D2.
3. The method of claim 1 , wherein said exposure is less than or equal to a therapeutically effective dose.
4. The method of claim 1 , wherein said exposure is at 50% or less of the therapeutically effective dose.
5. The method of claim 1 , wherein said normal tissue sample is of the same type as said subject sample with said disorder.
6. The method of claim 1 , wherein said subject sample is exposed to said genotoxic anti-neoplastic agent in vivo or in vitro.
7. The method of any one of the preceding claims, wherein said genotoxic anti-neoplastic agent is selected from the group consisting of 1,3-bis(2-chloroethyl) -1-nitrosourea, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, daunorubicin, doxorubicin, epirubicin, etoposide, idarubicin, ifosfamide, irinotecan, lomustine, mechlorethamine, melphalan, mitomycin C, mitoxantrone, oxaliplatin, temozolomide, topotecan, and ionizing radiation.