And Sunday, there was no stopping the Indianapolis Colts.
cancer-stricken Coach Chuck Pagano watching from a local hospital, overcame an 18-point deficit at home to pull off an unforgettable 30-27 upset of Green Bay.
"We're just so happy for Chuck," said rookie quarterback Andrew Luck, who completed 31 of 55 passes for 362 yards with two touchdowns and an interception. "Hopefully, this uplifts him in some sense or some fashion. I'm happy to be a part of this moment with this franchise."
What began with an email — a motivating message from Pagano to his team — ended with an airmail, a four-yard toss from Luck to Reggie Wayne for the go-ahead touchdown with 35 seconds left.
But the game wasn't quite over. The Packers came back and moved into position to tie. But with three seconds left, Green Bay's Mason Crosby was wide on a 51-yard field-goal try.
Pagano noticed this summer that he was especially fatigued and bruised easily, but he didn't take time to get it checked out until last week, when the Colts were on their bye. Doctors ran a battery of tests on him and determined he had leukemia, immediately admitting him to the intensive care unit of an Indianapolis hospital.
"My condition will not determine my position," Pagano, who celebrated his 52nd birthday Tuesday, wrote to his players. "I understand the condition but choose to focus on my position. That is to stay positive and serve. We will, we can, we must. We have no choice. By any means necessary. We will overcome."
Against the Packers, that meant clawing their way out of a 21-3 hole in the second half. Leading the charge was Luck, the former Stanford star who is remarkably poised for a player of any age, let alone a rookie.
Bruce Arians, himself a cancer survivor, was promoted from offensive coordinator to interim coach. He knows the Packers well, as he was offensive coordinator in Pittsburgh when the Steelers played Green Bay in the Super Bowl. In honor of Pagano, Arians' players wore T-shirts reading "Chuckstrong" — a variation of Lance Armstrong's "Livestrong" — and even Packers players wore them before Sunday's game.
Wayne wore orange gloves, rather than the pink ones signifying breast cancer awareness month, because orange is the color for leukemia patients.
"I just wanted to do something, you know, for Chuck," Wayne said. "I had some equipment guys make some calls."
The Luck-to-Wayne connection accounted for 13 receptions and 212 yards, and bridged two eras, the No. 1 overall pick hooking up with Peyton Manning's longtime go-to receiver.
The Colts were seven-point underdogs, and the game pitted teams that were at opposite ends of the performance spectrum last season. The Manning-less Colts were 2-14. The Packers were 15-1.
Luck is the first rookie to pass for more than 1,200 yards (1,208) and lead his team to at least two victories in his club's first four games. He and Carolina's Cam Newton are the only players to pass for at least 300 yards in three of their first four NFL games.
After Sunday's emotional victory, Arians said of Luck: "I wouldn't trade him for anyone in the universe."
Sacked and smacked
Tough day for a couple of quarterbacks.
Washington's Robert Griffin III and Kansas City's Matt Cassel were knocked out of their games after absorbing shots to the head.
The Redskins said Griffin sustained a mild concussion when he was hit midway through the third quarter. On third and goal at the three-yard line, he rolled right against Atlanta and tried to tuck the ball and run. While in the process of sliding toward the sideline, he was drilled in the head by Falcons linebacker Sean Witherspoon. It was a legal hit because Griffin was technically a runner at the time, and the play was recorded as a sack for a loss of two.
Griffin lay face down on the turf for a few moments before groggily climbing to his feet and walking slowly across the field to the Washington sideline. He sat on the bench, where the medical staff stitched his chin. He was walked to the locker room, briefly reemerged, then headed back inside.
"When he wasn't really sure what the score was, what quarter it was, we knew he had a mild concussion," Redskins Coach Mike Shanahan said.
Cassel was injured when hit by Baltimore's Haloti Ngata while completing a pass in the fourth quarter.
The Chiefs quarterback had four turnovers against the Ravens, and some in the crowd at Arrowhead Stadium cheered when he lay hurt on the turf.
Kansas City tackle Eric Winston said he was sickened by that fan reaction.
"We are athletes. We are not gladiators," Winston said. "This isn't the Roman Colosseum. People pay their hard-earned money to come in here. I believe they can boo, they can cheer, they can do whatever they want. . . .
"But when you cheer somebody getting knocked out, I don't care who it is, and just so happened to be Matt Cassel, it's 100% sickening. I've been in some rough times on some rough teams; I've never been so embarrassed in my life to play football, than at that moment right there."
After losing at Minnesota, the San Francisco 49ers regrouped for a week in Youngstown, Ohio, a planned layover on their way to New York for a game against the Jets.
Apparently, the 49ers found some answers there.
Since, they've outscored the Jets and Buffalo Bills by a combined 79-3, and Sunday the 49ers rolled up a franchise-record 621 yards.
Atlanta . . . and also-rans
It's only October, and the Falcons are already running away with the NFC South. They are 5-0 for the first time in franchise history, and no one else in the division has more than one victory.
After blowing leads and losing in overtime in consecutive weeks, the Dolphins finally slammed the door on an opponent, securing a 17-13 victory at Cincinnati with a late interception.
Rookie quarterback Ryan Tannehill played turnover-free football and notched a 92.3 passer rating, the best of his young career.
Miami's defense hasn't allowed a 100-yard rusher in 19 games.
Pittsburgh's defense played well in a 16-14 victory over Philadelphia, but the Steelers had some significant injury setbacks in the opening quarter.
Safety Troy Polamalu, who had missed the previous two games because of a calf strain, again left because of a calf injury. Outside linebacker LaMarr Woodley, who missed six games last season because of a hamstring injury, encountered the same problem Sunday and had to leave.
With their 41-27 blowout of Cleveland, the New York Giants have won eight consecutive games against AFC teams, including a victory over New England in Super Bowl XLVI.
Still remaining on the Giants' schedule is the rest of the AFC North, with upcoming games against Pittsburgh (Week 9), Cincinnati (Week 10) and Baltimore (Week 16).
Next stop: Canton
If win-loss records were kept for quarterbacks the way they are for pitchers, Tom Brady would be 9-4 in games against Manning, counting New England's 31-21 victory over Denver.
Sunday's game was only the second pitting quarterbacks who have presided over 125 victories in their careers, the first coming in 1998 when Dan Marino's Dolphins played John Elway's Broncos.
The Associated Press contributed to this report.