Resistance to chemotherapy is one of the greatest challenges in pancreatic cancer treatment. However, US researchers have found that inhibiting the enzyme TAK-1 can overcome this.
Once the researchers had developed a drug to inhibit the enzyme, they tested it in combination with gemcitabine, oxaliplatin and SN-38 (a metabolite of irinotecan). The TAK-1 inhibitor increased the sensitivity of pancreatic cancer cells in culture to all three anticancer drugs, enabling the use of doses that were up to 70 times lower than those required in controls to kill the same number of cancer cells.
Further study in mice showed that combining the TAK-1 inhibitor with very low doses of gemcitabine resulted in a 78 per cent reduction in tumour volume and prolonged survival. Use of gemcitabine alone against the cancer in mice was ineffective.
Melisi D, Xia Q, Abbruzzese JL et al. TGF-beta-activated kinase 1 (TAK1) is an in vivo druggable target for reverting pancreatic cancer chemoresistance. Abstract O-1002. Eur J Cancer Suppl 2009;7(2):87
Originally published in the December 2009 edition of MIMS Oncology & Palliative Care.