University System of Maryland

Stc.unm

Alan Edward Tomkinson

Alexander D MacKerell, Jr

Gerald M Wilson

Barbara Dziegielewska

Shijun Zhong

Feyruz Rassool

Helen Xi Chen

Hiroshi Ide

Xi Chen

Yoshihiro Matsumoto

In one embodiment, the invention provides a method of treating a subject who suffers from a neoplasm (including a cancer such as a radiotherapeutic-resistant cancer) by administering to the subject a therapeutically effective amount of (a) 5-formyl-2'-deoxyuridine (fdU or foUdR) or a 5-formyl-2&#x2032;-deoxyuridine derivative, optionally in combination with 5-hydroxy-2&#x2032;-deoxyuridine (hUdR); and (b) at least one composition selected from the group consisting of either 5-fluorouracil (5-FU), a 5-FU prodrug (e.g. 5-fluoro-2&#x2032;-deoxyuridine (FdU)) or 5-FU metabolite. In a preferred embodiment, a subject who suffers from colorectal cancer (CRC) or metastatic colorectal cancer (mCRC) is treated with a therapeutically-effective amount of fdU and either 5-FU or the 5-FU prodrug 5-fluoro-2&#x2032;-deoxyuridine (FdU). Related pharmaceutical compositions are also provided.

Synergistic enhancement of 5-fluorouracil cytotoxicity by deoxyuridine analogs in cancer cells

Methods for treating cancer using compounds that inhibit human DNA ligases. Methods for using compounds that inhibit human DNA ligases to provide insights into the reaction mechanisms of human DNA ligases, for example to identify the human DNA ligase involved in different DNA repair pathways. Screening methods for compounds that inhibit human DNA ligases.

Compounds that inhibit human DNA ligases and methods of treating cancer

In one embodiment, the invention provides a method of treating a subject suffering from a breast cancer tumor which is non-responsive or intrinsically resistant to anti-estrogen therapy comprising administering a therapeutically effective amount of an inhibitor of alternative (ALT) non-homologous end joining (NHEJ) factor to the subject. In another embodiment the invention provides a method of treating a subject who suffers from a pancreatic cancer which is non-responsive to chemotherapy and/or radiation comprising co-administering a therapeutically effective amount of PARP1 inhibitor and a DNA ligase III&#x3b1; inhibitor to the subject. Related diagnostic methods, nucleic acid arrays, devices and kits are also provided.

Targeting abnormal DNA repair in therapy-resistant breast and pancreatic cancers

Growing community of inventors

Albuquerque, NM, United States of America

Alan Edward Tomkinson