LOS ANGELES - When James Cameron's Titanic hit theaters 12 years ago, it seemed like an enormous risk. The romance/disaster flick, which ran way over budget, ended up costing an eye-popping (for 1997) $200 million to produce and no one was sure the film would have broad enough appeal to earn its money back.

Of course Titanic went on to become the highest-grossing movie of all time, raking in almost $2 billion at the box office. After that triumph, Cameron went into semi-retirement, surfacing occasionally with documentary shorts like Ghosts of the Abyss and Aliens of the Deep.

Now he's back with what might be an even bigger risk: Avatar, the most highly anticipated film of the year. Cameron has spent years developing lightweight 3-D cameras and advanced motion-capture technology to realize his vision. The film, about a group of humans fighting on a faraway planet, cost an estimated $200 million to produce.

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The hype surrounding Avatar puts James Cameron at the top of our list of people who have the most to gain (or lose) at the box office this fall.

At stake could be the future of live-action 3-D. Hollywood is holding its breath to see if the movie can capture a mass audience beyond the kids who typically flock to 3-D animated films. If it's a hit, expect a flood of live-action 3-D movies.

Avatar is also crucial for Cameron's career. The reclusive director needs a massive hit to prove that he's still got what it takes to produce compelling and entertaining sci-fi movies like Aliens and Terminator.

So far the buzz has been mostly good. In August Cameron released a 16-minute preview of the film, which screened exclusively at Imax theaters for one night. Fans called the footage "impressive" and "amazing." But others have voiced skepticism about the 2-D trailer. A popular spoof video on YouTube shows Hitler ranting about how bad the trailer looks.

Coming in second on our list behind Cameron is George Clooney. The movie star is having a bit of a dry spell. His Ocean's movies are still hits at the box office, but since the last one hit theaters in 2007, Clooney has appeared in a string of box-office duds. Leatherheads, which Clooney also directed, earned only $41 million at the worldwide box office. The actor was nominated for the best actor Oscar for his work in Michael Clayton, but the film earned only $93 million. His box-office performance has left many wondering if Clooney can still open a movie.

He may be poised to shore up his movie-star status with Up in the Air, about a corporate consultant who specializes in layoffs, which hits theaters in November. The film is already earning buzz as a sure Oscar contender, and it seems like it might have some real box-office potential too. Director Jason Reitman's last film was Juno, which earned $230 million. If Up in the Air is a similar-size hit, it would help Hollywood justify Clooney's recent offbeat choices including his other fall film, The Men Who Stare at Goats, about a paranormal division of the U.S. Army. If that film also hits at the box office, Clooney will be this year's big winner.

Third on our list are Harvey and Bob Weinstein. The brothers have been the subject of much speculation in Hollywood because of their faltering production company. The recent strong performance of Inglourious Basterds ($227 million at the worldwide box office so far) has given the brothers something of a reprieve. But they could stand at least one more hit this year.

Nine, a film version of the Broadway musical starring Daniel Day-Lewis, is the company's big Oscar contender this year. The brothers are hoping it will replicate the success of Chicago, which they released in 2002. That movie earned $307 million at the box office and six Oscars. Chicago director Robert Marshall also directed Nine, so expectations are high.