Karl Rove wrecked his career when he twisted his arm to endorse Arlen Specter.
Unfortunately, Rove was an absolute jerk. He withheld support from Bill Simon in California, running against Gray Davis, and Simon lost by around 3%. No campaign funds, as the new head of the California GOP installed by Rove refused to raise any for him. Then Rove stepped in again, and we got Arnie, instead, after conservatives recalled Gray Davis.
Santorum had previously won a couple of races, but they were very close. He was too conservative for the state’s voters at that time to make it easy. So, Rove basically gave him a no-win offer. Refuse the endorsement, and you get no money or support. And, as it turned out, endorse Spectre and the conservative base stays home.
Santorum justified it by the fact that Arlen had earlier endorsed him. In any case, Rove managed to kill another Republican seat with his RINO stupidity.