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A lamb at school


If you've been following my blog posts, you've probably guessed that I'm fairly new to the subject of cancer. That means that each day brings more questions than answers. Today, for example, I attended a presentation entitled, "The Hedgehog Signaling Pathway: Biology and Therapeutics." Huh? I had heard about the "hedgehog pathway" before, but I thought it referred to the areas of the garden frequented by the insect-loving mammal. Today I learned otherwise.To understand the hedgehog pathway, you have to start with shepherds in Idaho. Just more than 50 years ago, they discovered that pregnant sheep that mistakenly grazed on the corn lily gave birth to lambs with cyclopia--a condition that left them with only one eye in the center of their foreheads, like the Cyclops. The corn lily contains a natural toxin, an alkaloid called cyclopamine, that's very similar to cholesterol.Cholesterol, as you've probably heard, will "clog your arteries," but some cholesterol, by incorporating into your cells' outer membranes, also serves the useful purpose of making them watertight. Moreover, cholesterol plays an important role in the "hedgehog signaling pathway" that controls early development of the embryo. In fact, cholesterol is responsible for processing the hedgehog protein to its mature, active form, by becoming physically attached to the protein.As embryos develop, the cells that determine different body parts get regulated through the hedgehog signaling pathway, a name derived from a stubby, spiny protein humans have in common with fruit flies. Yet when you introduce hedgehog to cyclopamine, hedgehog thinks it's meeting cholesterol, and instead of a harmonious love affair, cyclopamine and hedgehog have a dysfunctional relationship, resulting in complete distortion of the regions that dictate where the eye(s) get placed. The result: Cyclopia.Fast-forward to contemporary cancer research. In the 1970s, scientists learned that the hedgehog signaling pathway not only played a developmental role in mammals, regulating limbs and brain development in embryos, but also controlled the division of adult stem cells and several types of cancer cells. If researchers could "manage" the courtship of cyclopamine and hedgehog, perhaps they could stop cancer from developing.Today's presentation focused on how the inappropriate or "dysfunctional" activity of the hedgehog signaling pathway has been genetically linked to initiation and growth of cancers such as basal cell carcinoma and medulloblastoma, as well as the drug development activity that has focused on therapy of these cancers with agents that mimic the action of cyclopamine. Cutting edge? You bet.

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