Dana Reeve, actress and widow of Superman actor Christopher Reeve, has died of lung cancer.
Dana Reeve campaigned in favour of stem cell research
Reeve, 44, who led the Christopher Reeve Foundation, was diagnosed with the disease in August 2005.
She took over the organisation, which he founded, after his death. Reeve cared for her husband for nine years after he was paralysed in an accident.
Reeve, a non-smoker all her life, died on Monday, the foundation's president and chief executive Kathy Lewis said.
"We are extremely saddened by the death of Dana Reeve, whose grace and courage under the most difficult of circumstances was a source of comfort and inspiration to all of us," Ms Lewis said in a statement.
Reeve was a singer when she met her husband. They married in 1992 and celebrated the arrival of son Will in the same year. Christopher Reeve also had two grown-up children from his first marriage, called Matthew and Alexandra.
Three years later after their marriage, Christopher Reeve suffered a riding accident and was left paralysed from the neck down.
Reeve played Superman in four films before his accident
Dana Reeve devoted her life to his care, and immediately gave up her career.
Her acting credits included guest appearances in police dramas Law And Order and Feds.
She also played Wendy Schulz in a number of episodes of prison series Oz.
Reeve took over her husband's work at the foundation after his death in October 2004 at the age of 52 from an infection resulting from a pressure wound.
In November last year, she said she was responding well to treatment.
Former President Bill Clinton and Senator Hillary Rodham Clinton said Reeve was "a model of tenacity and grace".
"Despite the adversity that she faced, Dana bravely met these challenges and was always an extremely devoted wife, mother and advocate. Dana was an inspiration to us and we will miss her," the Clintons said.
Senator Diane Feinstein said of Reeve: "I thought that after everything that she had gone through with Chris that she would have time to smell the flowers and be in the sun. But apparently that was not meant to be."
Actress Catherine Zeta Jones, a supporter of the foundation, said of Reeve recently: "She's better than Superwoman, she's Wonder Woman. Dana is like a saint to me."