By some estimates, the war on cancer has been a colossal flop. But that hasn’t discouraged pharmaceutical companies from continuing to search for effective ways to treat this elusive killer.  The financial rewards are too just too attractive.

The challenge for investors is to figure out which company is going to cross the finish line with the big winners.

In terms of sheer size and scope, Pfizer (NYSE:PFE) looks like the No. 1 seed in the cancer research tournament. At its facility in San Diego, the company has some 1,000 researchers devoted to finding and developing new cancer drugs. Its goal is to reach $11 billion in sales of cancer drugs by 2018. That would be more than four times the category’s sales last year of $2.5 billion, which represented only 5% of Pfizer’s revenue.

The company desperately needs a successor to its blockbuster cardiovascular drug Lipitor, which loses patent protection this year.

Perhaps Pfizer has the answer in Crizotinib, one of its more than 20 new tumor-fighting medicines the company is studying.  The lung cancer treatment is expected to be the first of three Pfizer cancer drugs submitted for approval this year. Industry analysts say sales of Crizotinib could reach $755 million by 2015.

Amgen (Nasdaq:AMGN), on the other hand, went the acquisition route to get a promising cancer candidate. The company bought privately held BioVex earlier this year, primarily to get its hands on the cancer vaccine OncoVex, which is in the final stages of testing for the treatment of a skin cancer. The drug also is being studied in head and neck cancer.

A number of smaller companies are also chasing the proverbial pot of gold. Onyx Pharmaceuticals (Nasdaq:ONXX) saw its share price jump after the FDA said it would fast-track the company’s cancer drug Carfilzomib for treating the second-most common blood cancer, multiple myeloma.

Others with potentially game-changing cancer drugs in their portfolio include:

• Ariad Pharmaceuticals (Nasdaq:ARIA), whose ponatinib in a midstage trial as a treatment for two types of blood cancer. Ariad is trying to develop ponatinib as a treatment for patients who are resistant or intolerant to other treatments.
• Seattle Genetics (Nasdaq:SGEN) hopes to have approval later this year of its monoclonal antibody brentuximab vedotin that targets Hodgkin lymphoma. About 8,500 cases of Hodgkin lymphoma were diagnosed in the U.S. during 2010 and more than 1,300 died from the disease
• Aveo Pharmaceuticals (Nasdaq:AVEO) is testing a renal cancer drug with blockbuster potential. However, the company is short on cash and its coffers may run dry before it can get tivozanib to market in 2013. This makes the company an ideal acquisition candidate.
• Exelixis (Nasdaq:EXEL) is another takeover target given its potential for financial distress and the promise of it prostate cancer drug cabozantinib.

Investors who believe the past is prologue might want to temper their enthusiasm about companies with cancer treatments.  Cancer is an incredibly complicated disease. As one biologist pointed out, it could even be hundreds or thousands of diseases. And the same drug may be effective with one person with a type of cancer and not another. 

Always looming, too, is the big question of who’s going to pay for drugs that may cost upward of $50,000 a year and only marginally extend someone’s life.