My advice to you if you think you're writing a hybrid book is to be bold and carry on. Chances are you're an outside-the-box kind of thinker, and with that quality under your belt, you'll find your way to your readers, or your readers will find you.
Remember that an agent who wants to represent you is courting you. Allow yourself to be courted; don't throw yourself at the first prospect that comes along and agree to make changes you don't really want to make. Be flexible; don't be a doormat.
The hard truth is that most of us do not have that shiny quality that agents and editors are looking for. And it's not your fault if you don't. That allure is something that generally takes years to build and grow.
This week, the Big Five just got bigger with the announcement that Hachette Book Group (the fourth largest U.S. publisher) is acquiring Perseus Books Group (the sixth largest U.S. publisher) in a deal that will close next month.