Cancer research blow after U-turn

OUR BUREAU AND REUTERS

Jan. 10: A cascade of study retractions by an India-born and educated oncologist and his colleagues in the US has shaken the cancer research community and forced a revision of research aimed at tailoring treatment to the genetic profiles of patients.

The oncologist Anil Potti, now at the Coastal Cancer Center in Myrtle Beach, South Carolina, and his co-authors retracted on Friday a 2008 study from the Journal of the American Medical Association that described genetic signatures to individualise chemotherapy in breast cancer.

Potti, who was born in Hyderabad and studied medicine at the Christian Medical College, Vellore, before moving to the US, had been studying genetic signatures to predict response to chemotherapy and thus help tailor individualised treatment strategies.

Potti and his co-authors have withdrawn eight papers from various journals since July 2010 when the North Carolina Medical Board first received information about possible misconduct related to his research at the Duke University Medical Center in North Carolina where he was working at the time. The Duke Medical Center is currently conducting a misconduct inquiry on the work of Potti who resigned from his position there in December 2010.

Duke University has closed clinical trials based on his research and, according to a cancer newsletter in the US, is now facing lawsuits from participating patients. Senior oncologists are worried about the fallout of the affair on patient-doctor equations in the US.

"There are a lot of people in the US who do not trust doctors and sometimes take wrong medical decisions. We fear that this incident has, unfortunately, reinforced this distrust," said Otis Brawley, chief medical officer of the American Cancer Society.

"I think this should lead to some soul-searching about our current system of oversight into research," Brawley told The Telegraph over the phone. "Our mechanisms for investigating scientific misconduct need to be strengthened."

After Potti's resignation in December 2010, Duke University had issued a statement stating that his collaborator Joseph Nevins had initiated a process intended to lead to a retraction request of a paper published in the journal Nature Medicine in 2006. The retraction notice said that the researchers were "unable to reproduce certain crucial experiments".

Potti was not available for comment. A call to the Coastal Cancer Center was not returned. A media release issued on his behalf on Friday — the day of the latest retraction — described him as "a thorough clinician" and "successful medical professional" who specialises in providing thorough care and services to lung cancer patients.

The release said he is certified in oncology, "possesses strong family values", and involves himself in a large number of social welfare activities, regularly contributing a significant amount of time and money to the school system and the local church.

Brawley, who is also professor of oncology at Emory University in Atlanta, Georgia, said studies to determine how genetic profiles of individual patients can influence response to chemotherapy remain a "legitimate and important area of research".

Keith Baggerly, who studies genomics at the M.D. Anderson Cancer Center in Houston, has been looking into the Duke team's data since shortly after the Nature Medicinereport came out. A colleague approached Baggerly and Kevin Coombes, another M.D. Anderson researcher, hoping the work could help improve the treatment of patients.

But Baggerly and Coombes found numerous problems in the research, including mislabelling of data. They asked the Duke researchers for their data but they were slow to provide it. Eventually, some journals published the critiques, often alongside defences of the work by Potti and his colleagues. Meanwhile, clinical trials using the genetic signature continued at Duke.

Baggerly's questions went largely unheeded until July 2010, when The Cancer Letter, a trade publication, reported that Potti had falsely claimed to be a Rhodes Scholar on an American Cancer Society grant application. Within months, the trials were halted, and Duke returned $729,000 to the cancer organisation.

An oncologist said the research had been used to guide chemotherapy strategies in a number of patients. The Cancer Letter said in the trials, "patients were assigned chemotherapy based on genomic predictors" developed by Potti and his team.

For plaintiffs' attorneys, proving that patients were actually harmed by being in the trials will be difficult, said Brawley. "I don't myself think that patients were harmed by being steered to a particular chemotherapy, at one level," Brawley said. The choices in the trial were widely accepted therapies that their own doctors would have likely given them, Brawley said.