Beau Biden -- son of Vice President Joe Biden -- died of brain cancer at 46, the White House confirmed in a statement Saturday.
"It is with broken hearts that Hallie, Hunter, Ashley, Jill and I announce the passing of our husband, brother and son, Beau, after he battled brain cancer with the same integrity, courage and strength he demonstrated every day of his life," the statement from Vice President Biden's office said.
"The entire Biden family is saddened beyond words. We know that Beau's spirit will live on in all of us-especially through his brave wife, Hallie, and two remarkable children, Natalie and Hunter," the statement said.
President Obama said he and the first lady 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 statement released late Saturday.
Beau Biden was a lawyer and member of the Delaware National Guard and former Delaware attorney general. However, he never would follow in his father's footsteps as a U.S. senator.
Biden, although planning to run for governor of Delaware in 2016, was plagued with health troubles throughout his political career.
In 2010, Biden suffered a mild stroke at only 41 years old. Three years later, he found himself in a Texas hospital for cancer treatment.
In August 2013, he would undergo surgery at MD Anderson Cancer Center at the University of Texas in Houston to remove a lesion. That was followed by radiation treatment and chemotherapy. Three months after the procedure, doctors gave him a clean bill of health.
However, Biden suffered a recurrence and was admitted to Walter Reed Hospital in May, officials said. At that time though, it was unaware why he was being treated.
Support for the Biden family poured in from both sides of the aisle Saturday night into Sunday morning.
Democratic presidential contenders Hillary Clinton and Martin O'Malley both expressed their sympathies to the Bidens.
“My heart is broken for the family of Beau Biden -- a wonderful man who served his country with devotion and lived his life with courage," Hillary tweeted.
“Katie and I are deeply saddened by the news of the passing of Beau Biden. He served his country and the people of Delaware with great honor," O'Malley said in a statement. “Our thoughts and prayers go out to the entire Biden family in this moment of great loss."
Senator James Langford (R-OK) also released a statement expressing his remorse.
"I'm incredibly saddened to hear of the death of Vice President Joe Biden's son, Beau Biden," the statement said. “Our entire nation mourns with the Biden family and the White House during this difficult time. Vice President Biden has endured incredible tragedies during his lifetime. Cindy and I pray for the Biden family, Beau's widow, Natalie, and their two children."
The news of Beau Biden's death also caught the Delaware political establishment off guard and also renewed questions about his health. Beau Biden kept a low profile and declined any interviews abou his health.
"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 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."
Gordon said he last spoke to Beau several weeks ago, when Biden participated in a conference call on crime issues in Wilmington.
"He was a rock star," Gordon said. "He had a great image, great character."
Beau Biden left office earlier this year and joined a Delaware law firm run by Stuart Grant, a prominent Democratic campaign donor and plaintiffs lawyer specializing in corporate litigation. The first announced in late April that Biden was expanding his work on behalf of whistleblower clients, but was not available to clients.
Biden, a University of Pennsylvania graduate, earned a law degree from Syracuse University in 1994. He served as a law clerk for a federal judge in New Hampshire before working for the U.S. Department of Justice from 1995 until 2002, including five years as a federal prosecutor in Philadelphia. In 2001, he volunteered for an interim assignment helping to train judges and prosecutors in postwar Kosovo.
With his father, then Delaware's senior U.S. senator, at his side in 2006, Biden launched his campaign for attorney general. He promised to reorganize the state Department of Justice to better combat identity theft, Internet stalking by pedophiles, street crime and abuse of the elderly.
Biden won with 52.6 percent of the vote.
"He's supped at this table since he's been 3 years old," a beaming Joe Biden said after the victory. Beau Biden was a toddler when his father was first elected to the Senate.
"I'm just proud of him," the elder Biden added. "I think he will make the state proud."
The young Biden sidestepped questions about his own political ambitions during the campaign.
"Sometimes, it's not good to look too far down the road," said Biden, who remained similarly cautious about discussing his long-range plans in an interview with The Associated Press after suffering the stroke in 2010.
"Having long-term dreams is a good thing ... but having a plan has never worked for me, because life always intervenes," Biden told the AP at the time. For Biden, his initial health scare was also a reminder to balance his job with family time — advice he encouraged others to follow.
"It's kind of reinforced how I've operated my life," he said.
As attorney general, Biden established a child predator unit, joined other attorneys general in taking on mortgage lenders over foreclosure abuses, proposed tougher bail restrictions for criminal defendants, putting him at odds with some fellow Dems.
But a spate of shootings in Biden's hometown of Wilmington went largely unabated during his tenure, and his office stumbled in some high-profile murder prosecutions, including two cases in which murder charges were dropped. Biden also faced scrutiny over how his office handled the case of Earl Bradley, a pediatrician who sexually assaulted scores of young patients over more than a decade before being arrested in December 2009.
Biden cited his focus on the Bradley case in announcing in January 2010 that he would not run for the Senate seat that his father vacated in 2008 when he was elected vice president.
The younger Biden's decision stunned political observers, including many fellow Democrats who thought Joe Biden's former chief of staff, Ted Kaufman, had been appointed to the Senate on an interim basis to keep the seat warm for the son. A fellow Democrat, New Castle County Executive Chris Coons, won the seat after Castle, who had been considered the odds-on favorite, was upset by tea party-backed Christine O'Donnell in the GOP primary.
"I have no regrets," Biden said after O'Donnell's stunning primary victory scrambled the political calculus surrounding the Senate seat.
Biden coasted to re-election as attorney general in 2010 after Republicans declined to field a candidate against him.
In addition to his work as a lawyer and attorney general, Biden was a major in an Army National Guard unit that deployed to Iraq in 2008.
He was married and the father of two children.
Markell ordered flags to be flown at half-staff in Delaware in honor of Biden.
Funeral arrangements are pending.
Fox News' Shannon Bream, Hillary Vaughn, Serafin Gomez and The Associated Press contributed to this report.