In addition to adding promising - though still risky - experimental medicines known as immunotherapies that boost the body's immune system to fight tumours, acquiring AstraZeneca could also generate significant cost savings, according to industry analysts.
As a result, a deal at around a 25 percent premium to the current share price funded by cash, cheap debt and some stock could boost Pfizer earnings immediately, they believe.
Both companies have declined to comment on a report in the Sunday Times, which cited senior investment bankers and industry sources saying that Pfizer approached the British pharmaceuticals group about a deal. The newspaper said no talks were currently under way after AstraZeneca resisted the approach.
Citi analyst Andrew Baum said he believed the report was "very likely genuine" and Pfizer could return to the fray, given the attractiveness of AstraZeneca's pipeline of cancer drugs, its expertise in autoimmune diseases and the scope for taking out costs.
"We anticipate Pfizer to push aggressively ahead with a second approach," Baum wrote in a research note on Monday, adding that AstraZeneca might seek to structure any deal as a merger of equals as a defence strategy.
Betaville, a British financial blog, on Monday said AstraZeneca had hired Goldman Sachs and Morgan Stanley to act as "defence" advisors in the event Pfizer makes a new effort to acquire the London-based drugmaker.
The two investment banks already act as AstraZeneca's corporate brokers.
The blog also said that Pfizer may be working with JP Morgan to work on any potential bid. AstraZeneca and Pfizer declined to comment on the investment bankers, and officials at Goldman Sachs and Morgan Stanley could not immediately be reached.
Pfizer shares closed up 2 percent, while AstraZeneca shares rose 8.8 percent, both on the New York Stock Exchange.
Pfizer has a long track record of making major acquisitions, with the $68 billion (40.5 billion pounds) purchase of Wyeth in 2009 its last major deal, after earlier acquisitions of Pharmacia and Warner Lambert.
The drugmaker has more recently been divesting certain operations and mega-mergers have fallen out of fashion in the pharmaceuticals industry following scepticism about how well some of them have worked. But Chief Executive Officer Ian Read has said he would still consider a large deal that made sense.
Read also has an incentive to buy assets overseas rather than in the United States since Pfizer has tens of billions of dollars accumulated through foreign subsidiaries, which if repatriated to the U.S. would be heavily taxed.
A Pfizer move on AstraZeneca might flush out other bidders. U.S. biotech giant Amgen Inc already has a tie up with AstraZeneca in autoimmune medicines to treat diseases such as psoriasis and severe asthma.
Novartis AG and larger GlaxoSmithKline Plc have also been mentioned in the past as potential suitors, although GSK has in recent years said publicly it is not interested in making a large acquisition, while Novartis is in the middle of strategic review and already has a presence in cancer immunotherapy.
Mark Schoenebaum, an analyst at ISI, agreed cancer immunotherapy was likely the main lure for Pfizer, since the field is expected to become one of the biggest areas of modern medicine in the next few years.
However, Mark Clark at Deutsche Bank said Pfizer would be making something of a "leap of faith" since AstraZeneca's most exciting cancer drugs are still at an early stage of development.
Pfizer has a highly promising breast cancer drug in late-stage development called palbociclib but otherwise its cancer portfolio is relatively weak.
"Notably, Pfizer appears to be nowhere in the important field of immuno-oncology, which Bristol-Myers Squibb, Roche, Merck & Co and AstraZeneca currently dominate," Schoenebaum said.
Bristol, Roche and Merck are viewed as being ahead of AstraZeneca in the new cancer field but the British firm believes it can make up ground by pioneering drug combinations, including the use of a medicine known as tremelimumab that it licensed from Pfizer.
AstraZeneca and its rivals will present the latest clinical data on promising new cancer drugs at the May 30 to June 3 annual meeting of the American Society of Clinical Oncology.
The London market was closed on Monday for Easter but the talk of Pfizer's interest in AstraZeneca is likely to overshadow dealings when trade resumes on Tuesday.
AstraZeneca Chief Executive Officer Pascal Soriot, who has been credited for progress in rebuilding the company's new drug pipeline since taking over in 2012, fuelling a rally in the shares, will also come under pressure to address the reported Pfizer approach when he presents half-year results on Thursday.
Speculation over such a takeover, which would be potentially the biggest ever foreign takeover of a British company, is likely to trigger concerns about jobs in Britain's pharmaceuticals sector, which is viewed as a key industry by the government but which has been under pressure.
AstraZeneca has already laid off thousands of scientists and other staff as it shrinks its cost base to cope with a fall in sales due to patent losses on blockbuster medicines.
With heartburn treatment Nexium losing U.S. patent protection next month and cholesterol fighter Crestor facing patent expiry in 2016, the decline in sales is expected to continue for several years.
In an attempt to reshape the company, Soriot is currently moving its research and corporate headquarters to Cambridge, England. Pfizer has also made the university city a research hub after shuttering a large research site in Sandwich, southern England.
The Cambridge connection is only one link between Pfizer and AstraZeneca, highlighting how the companies know each other well.
AstraZeneca's head of innovative medicines Mene Pangalos also used to work at Pfizer and the two firms are familiar with each other's products from working together on projects, such as a pioneering of a new kind of clinical trial for cancer drugs announced last week.
(Editing by Jane Merriman, David Holmes and Lisa Shumaker)
By Ben Hirschler