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Dover, Del. — He was the privileged son of a longtime U.S. senator and two-term vice president, yet Joseph R. “Beau” Biden III was no stranger to personal adversity.

When he was only 3, just weeks after his father, Joe Biden, had been elected to the Senate, the younger Biden was seriously injured in a 1972 car crash that killed his mother and infant sister. His father was sworn into office at his hospital bedside.

As a young college student, not long after his father’s 1987 presidential campaign imploded among allegations of plagiarism, he was back in the hospital, holding vigil with other family members as Joe Biden underwent surgery for a life-threatening aneurysm.

And after launching his own successful political career, Mr. Biden was dogged by health problems. In 2010, he suffered a mild stroke at the age of 41.

On Saturday, Mr. Biden died of brain cancer, less than two years after he was diagnosed. He was 46.

Although twice elected attorney general, the younger Biden never realized the dream of many Delaware political observers that he would follow in his father’s footsteps as a U.S. senator, and perhaps even become governor.

Mr. Biden did, in fact, plan to run for governor in 2016. He made the announcement in an April 2014 email to supporters in which he also noted he would not seek re-election as Delaware attorney general.

The announcement caught Delaware’s political establishment off guard, and also renewed questions about Mr. Biden’s health. In the ensuing months, he kept a low public profile and declined news media requests for interviews.

“I think he would have run. I think he would have won,” said Delaware Gov. Jack Markell, a fellow Democrat. Markell said he last spoke to Mr. Biden in February, when he invited him to a meeting of Democratic governors in Washington, D.C.

“He was serious” about running for governor, added New Castle County Executive Tom Gordon, a longtime friend and political ally of Joe Biden who described Beau Biden as the most popular politician in Delaware. “He thought he was going to win this battle.”

President Barack Obama said he and wife Michelle were grieving alongside the Biden family.

“Michelle and I humbly pray for the good Lord to watch over Beau Biden, and to protect and comfort his family here on Earth,” Obama said in a separate statement. The Obamas visited the vice president and his family at their official residence, the Naval Observatory, on Sunday afternoon.

After leaving office earlier this year, Mr. Biden joined a Delaware law firm run by Stuart Grant, a prominent Democratic campaign donor and plaintiffs lawyer specializing in corporate litigation.

In addition to his work as a lawyer and attorney general, Mr. Biden was a major in an Army National Guard unit that deployed to Iraq in 2008.

Mr. Biden is survived by his wife, Hallie, and children Natalie, 11, and Hunter, 9, along with his father and stepmother, a brother and sister, a sister-in-law and brother-in-law, and three nieces.

Funeral arrangements were not announced.

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