Highly Effective Therapies for Single Cancer Types Should be Expected in the Near Future

The trouble with cancer research is that all cancers are different; expensive and slow research results in only one therapy for one small group of cancer patients. Real progress would mean finding commonalities between many cancer types, or mechanisms essential to all cancer such as lengthening of telomeres. That is still a minority concern in the research community, but is growing thankfully in recent years. Nonetheless, since various types of cancer spring from specific mutations, it should be expected that with progress in biotechnology researchers will discover the basis for highly effective therapies for at least a few types of cancer:

Up to 90% of colorectal tumors contain inactivating mutations in a tumor suppressor gene called adenomatous polyposis coli (Apc). Although these mutations are thought to initiate colorectal cancer, it has not been clear whether Apc inactivation also plays a role in tumor growth and survival once cancer has already developed. This question has been challenging to address experimentally because attempts to restore function to lost or mutated genes in cancer cells often trigger excess gene activity, causing other problems in normal cells.

To overcome this challenge, researchers used a genetic technique to precisely and reversibly disrupt Apc activity in a novel mouse model of colorectal cancer. While the vast majority of existing animal models of colorectal cancer develop tumors primarily in the small intestine, the new animal model also developed tumors in the colon, similar to patients. Consistent with previous findings, Apc suppression in the animals activated the Wnt signaling pathway, which is known to control cell proliferation, migration, and survival. When Apc was reactivated, Wnt signaling returned to normal levels, tumor cells stopped proliferating, and intestinal cells recovered normal function. Tumors regressed and disappeared or reintegrated into normal tissue within 2 weeks, and there were no signs of cancer relapse over a 6-month follow-up period. Moreover, this approach was effective in treating mice with malignant colorectal cancer tumors containing Kras and p53 mutations, which are found in about half of colorectal tumors in humans.

Researchers continue to investigate why Apc is so effective at suppressing colon tumor growth, with the goal of one day mimicking this effect with drug treatments. "It is currently impractical to directly restore Apc function in patients with colorectal cancer, and past evidence suggests that completely blocking Wnt signaling would likely be severely toxic to normal intestinal cells. However, our findings suggest that small molecules aimed at modulating, but not blocking, the Wnt pathway might achieve similar effects to Apc reactivation. Further work will be critical to determine whether Wnt inhibition or similar approaches would provide long-term therapeutic value in the clinic."

Link: http://www.eurekalert.org/pub_releases/2015-06/cp-asg061115.php

Comments

The recent work by Blasco which targets the Shelterin protecting the Cancer cell Telomeres and thus removing it's immortality is very promising. I am hoping this can be applied broadly to most Cancers as they all share the common mechanic of Shelterin which can be attacked.

http://medicalxpress.com/news/2015-05-scientists-immortality-cancer.html

Also the CD47 therapy at Stanford is looking very promising

http://stemcell.stanford.edu/CD47/

If both can be developed they would offer a pretty broad range of treatment and both use interesting mechanics to work. Seems they are starting to think outside the box.

Posted by: Steve H at June 23rd, 2015 3:36 PM

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