Targeting NF-kappaB for colorectal cancer.
BACKGROUND
Colorectal cancer (CRC) is the second leading cause of cancer death. Progress has been made in the development of chemotherapy for advanced CRC. Targeted therapies against VEGF or EGFR are now commonly used. Many cases show that tolerance develops to such treatments and thus new strategies are required to replace or complement current therapies. The NF-kappaB signaling pathway plays critical roles in physiological and pathological processes, and the relationship between colon cancer development and NF-kappaB is becoming clear.


METHODS
We discuss evidence for the participation of activated NF-kappaB in carcinogenesis and consider the possibility of NF-kappaB being a target for CRC treatment.


RESULTS
NF-kappaB activation might be involved in development of not only colitis-associated cancer, but also sporadic CRC. NF-kappaB activation is associated with hallmarks of cancer. Constitutive NF-kappaB activation is frequently observed in CRC and is associated with angiogenesis and resistance to chemotherapy. Several NF-kappaB inhibitors have proven to be useful.


CONCLUSIONS
Induction of NF-kappaB activation leads to resistance to chemotherapy and constitutively activated NF-kappaB can often be seen in CRC. Anti-NF-kappaB therapy may rescue many cases of CRC and should be examined further for use as a therapy target.
Sakamoto
Kei
K
Institute for Adult Diseases, Asahi Life Foundation, Division of Gastroenterology,1-6-1 Marunouchi, Chiyoda-ku, 100-0005 Tokyo, Japan.
Maeda
Shin
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D016503:Drug Delivery Systems; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D016328:NF-kappa B