I was in medical school when Sally Ride, Ph.D, rode in space. Yesterday, I learned that she died of pancreatic cancer at the ripe age of 61 years. According to multiple reports, the physicist-astronaut had faced the disease for 17 months. She was a remarkable woman. Her case of pancreatic cancer was, unfortunately, typical in its course.
Pancreatic cancer is one of the few tumors with a rising incidence in North America, according to the American Cancer Society's (ACS) 2012 report. The most common form of the disease, called adenocarcinoma, arises from glandular cells in the main part of the pancreas. Nearly 44,000 people will receive a diagnosis this year, and over 37,000 will die from it. Pancreatic cancer ranks fourth among malignant killers in the U.S.
Scientific understanding of this tumor type lags, although several recent studies offer insights in its genetic underpinnings. A 2008 review attributes between 5 and 10 percent of cases to an inherited mutation or familial disposition. In most other affected individuals, pathologists find multiple acquired genetic aberrations in the cancer cells.
A recent publication in the ACS journal Cancer indicates that the rising incidence of pancreatic cancer -- on the order of 1 percent per year between 1999 and 2008 -- is mainly affecting Caucasian men and women. The only established risks are smoking tobacco and obesity; the cause for the increase is unknown. The statistics are bleak: In the latest ACS analysis, five-year survival was poor, in the range of five percent and, surprisingly, independent of the tumor stage at diagnosis; survival in the United States did not improve in the decade leading up to 2008.
Years ago, the only treatments for pancreatic cancer were surgery, to remove the tumor, and radiation. Surgery to the pancreas can be risky, especially in older patients. The digestive enzyme-containing organ is centrally located, near large vessels and easily inflamed. What's more, procedures like a Whipple -- in which all or part of the pancreas is removed -- are rarely curative. The problem, more often than not, is that by the time a person with pancreatic cancer or their doctor notices something's wrong, the tumor's already invaded nearby structures like the bile duct where it can cause obstruction, jaundice, and pain.
After surgery, some patients opt for an observational or palliative care approach. Treatments for pancreatic cancer after surgery include radiation and sometimes chemotherapy, typically with 5-fluorouracil (5-FU) and, in recent years, gemcitabine (Gemzar). So far the FDA has approved one targeted therapy, erlotinib (Tarceva) for treatment, in combination with chemotherapy, of advanced pancreatic tumors. This pill is an enzyme inhibitor; it blocks activity of the Epidermal Growth Factor Receptor (EGFR) and likely other signaling molecules aberrantly "turned on" in malignant cells. Like other drugs of its type, Tarceva is costly -- to the tune of $30,000 per year, and can be toxic.
Scientists have observed that a particular oncogene, a DNA element that turns cells cancerous, is activated in a high fraction of pancreatic tumors. The K-ras oncogene may prove a useful target for future therapies, but so far none are established. Pancreatic cancer was also notably one of the first tumor types for which therapeutic vaccines were tested. Trials are ongoing to see if immunization strategies may help patients with various stages of this disease.
Sally Ride's unusual career reflected progress in science, technology and, also, attitudes toward women. She was smart and not particularly risk-averse. She took a ride into space and she did so knowing the potential harms and benefits in her journey, an ambitious experiment of sorts. She set a lead with forward-but-responsible, grounded thinking of the sort that patients, doctors and researchers in oncology might follow, today.
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