We're currently running 4.7.0 and experiencing an issue with DNN interfering with HttpHandlers.  We are trying to use the newest version of the Telerik RadChart for ASP.NET AJAX (Q1 2008 - yes, we've fully upgraded our compiled copy of DNN to .NET 3.5 including ASP.NET AJAX) and it uses a handler called "ChartImage.axd".  When it renders the image for the chart, it uses that handler as the image source.  It does not work when it is trying to access ChartImage.axd from a path like the following: /Dashboard/tabid/82/ChartImage.axd, whicih is the only path it knows to use.  If I take the URL being used as the image source and remove everything from that path except ChartImage.axd, the image renders properly.  So, is something with friendly URLs interfering with HttpHandlers?  This is really causing some great grief and we cannot upgrade to 4.8.2 yet (if it's even fixed there), so we can't test a newer version.

You may just need to exclude "ChartImage" from compression, assuming you are not already excluding .axd, and assuming you are using compression.

You could try the Friendly Url Provider that I distribute : it's a replacement for the standard DNN Friendly Url Provider and works in the same way, but produces better Urls - but in your case, more importantly, it includes a regex filter to exclude whatever type of request you like from the DNN processing which is causing the problem.

You can read about it at the iFinity Friendly Url Provider for DotNetNuke product page.