Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport.

There has been a number of new studies that depict the Hedgehog Pathway as an important regulator of stems cells. More importantly it has been shown that it is an important regulator of metastasis or movement of cells. In the case of cancer this is often deadly. Hh inhibitors namely cyclopamine has been shown to stop metastasis from a leukemias to solid tumors. As some of you might know Genentech filed an IND for a systemic Hh inhibitor for metastatic cancers.

In a number of studies Hedgehog Pathway inhibitors have shown to have no effect on some cancer cell lines. For example in pancreatic cancer cells lines Hedgehog Pathway inhibitors work on about 25% of them. However, what studies are showing that inhibiting the Hh pathway and a few other pathways at the same time has a synergistic effect to kill cancer cells. When studies have combined up to three drugs to target the same cell line all the drugs when combined with a Hh inhibitor had a significant effect in killing the cancer cells. Interestingly most of these cancer cells had no effect when subjected to a Hh inhibitor alone.

A current motif in cancer resistance has been demonstrated that cancer cells actually learn how to pump out these drugs and become resistant to current therapies. This has been a major delima for cancer drug design. A new study demonstrated that when the Hh pathway is blocked drugs are not permitted to leave the cancer cells and thus build up and cause it to die. This could be one reason why when an Hh inhibitor is used on certain cell lines and show to have no effect by itself but show significant effect when adding multiple inhibitors.

http://www.pathway2curis.com/sonic-hedgehog-promotes-multiple-drug-resistance-by-regulat-vt8378.html
http://www.pathway2curis.com/blockade-of-hedgehog-signaling-inhibits-pancreatic-cancer-i-vt8000.html
http://www.pathway2curis.com/targeted-therapy-for-cancer-stem-cells-the-patched-pathway-vt7788.html
http://www.pathway2curis.com/combined-targeting-of-epidermal-growth-factor-receptor-and-vt8509.html