Grant: Project Grant

Blood cancer (leukemia) is common, with ~55,000 new cases expected in the United States and Canada in 2019. The National Cancer Institute (US) calculated an overall 5-year survival rate of 56% for various blood cancers. This is because drug resistance and relapse pose significant challenges. Life-long treatment is required, with potential side-effects and a high cost. Blood cancer cells generally respond to drug therapy at the onset, but the drugs lose their effectiveness after 6-12 months. We and others have discovered that this is mainly due to the inability of current therapies to eradicate blood cancer stem cells, which maintain the potential for relapse. There is thus an urgent need to develop new therapies that specifically target blood cancer stem cells, so that these cells can be eliminated, leading to a cure. However, there are currently no drugs that directly target blood cancer stem cells in a specific and potent way, nor any related drugs that are approved as therapeutics. Interestingly, we have recently discovered that PAK6, a novel drug target, displays abnormal activity in blood cancer stem cells, particularly in drug-resistant patients, compared to drug-sensitive patients. We have found that combining a PAK6 inhibitor with current anti-cancer drugs, to target abnormal activities of PAK6, more effectively inhibits blood cancer stem cell growth in culture than single drug treatment; this treatment strategy also doesn't have side-effects on normal blood stem cells, which provides a therapeutic window specifically for anti-cancer treatment. This study will investigate if this combination therapy will more effectively eradicate blood cancer stem cells obtained from drug-resistant patients and prevent blood cancer development, using our newly established animal cancer models. This work will provide ultimate proof-of-concept for the development of more effective therapies, with fewer side effects than currently used therapies.