REPLICATION FACTOR C-40 (RFC40/RFC2) AS A PROGNOSTIC MARKER AND TARGET IN ESTROGEN POSITIVE AND NEGATIVE AND TRIPLE NEGATIVE BREAST CANCER

摘要

The present disclosure relates generally to cancer and particularly to breast cancer including estrogen sensitive, estrogen resistant and triple negative breast cancer (TNBC), and to methods of diagnosis and prognosis thereof and therapeutic intervention involving replication factor C 40 (RFC40). Methods and assays for evaluating breast cancer are provided. The disclosure also relates to inhibition or modulation of RFC40 in treatment or alleviation of cancer, including breast cancer. RFC40 inhibitors, including siRNAs, miRNAs, and shRNAs, which specifically affect cancer cells, particularly breast cancer cells, are provided.

主权项

1. A pharmaceutical composition for use in prophylaxis and/or therapy of cancer, the composition comprising one or more of:
i) a polynucleotide encoding an shRNA comprising the sequence of SEQ ID NO:21 (ACUACGAACUGCCGUGGGUUGNNNNNNNNNCAACCCACGGCAGUUCGUAGU); ii) a polynucleotide encoding an shRNA comprising the sequence of SEQ ID NO:24 (GUCCCGCUGUGCAGUCCUCCGGUACACAANNNNNNNNNUUGUGUACCGGAGG ACUGCACAGCGGGAC); iii) a polynucleotide comprising SEQ ID NO:18 (aCAGGUGAGGUUCCUGggagcc), iv) a polynucleotide comprising SEQ ID NO:19 (aCAGGUGAGGCUCCUGggagcc). v) a polynucleotide comprising the sequence of SEQ ID NO:21 (ACUACGAACUGCCGUGGGUUGNNNNNNNNNCAACCCACGGCAGUUCGUAGU), or vi) a polynucleotide comprising the sequence of SEQ ID NO:24 (GUCCCGCUGUGCAGUCCUCCGGUACACAANNNNNNNNNUUGUGUACCGGAGG ACUGCACAGCGGGAC).