Friday, January 13, 2012

Chemo drugs may lead to cancer relapse


Chemotherapy drugs, vital for putting the cancer into remission, may contribute to relapse of the disease in patients by damaging DNA, a new study has revealed.

Chemotherapy is known to damage the DNA of both cancer cells and healthy cells. But until now, scientists have had little direct evidence to suggest that chemotherapy itself helps shape the evolution of cancer cells and may contribute to disease recurrence.

The researchers suspect this phenomenon is not unique to acute myeloid leukemia (AML) and may occur in other cancers as well.

"The mutations in AML patients who have relapsed are different from those present in the primary tumour, and they are more likely to have a telltale signature of DNA damage," said senior author John F. DiPersio, MD, PhD, the Virginia E. and Sam J. Golman Professor of Medicine and chief of the division of oncology.

"This suggests that mutations in the relapse cells are influenced by the chemotherapy drugs the patients receive."

According to co-author Timothy J. Ley, MD, the Lewis T. and Rosalind B. Apple Professor of Oncology, chemotherapy drugs are absolutely necessary to get leukemia patients into remission, but 'we also pay a price in terms of DNA damage'.

"They may contribute to disease progression and relapse in many different cancers, which is why our long-term goal is to find targeted therapies based on the mutations specific to a patient's cancer, rather than use drugs that further damage DNA," Ley said

For the current study, scientists at Washington University's Genome Institute sequenced the genomes - the entire DNA - of cancer cells before and after relapse in eight patients with AML and compared the genetic sequences to healthy cells from the same patients.

The data essentially allowed them to map the evolution of cancer cells in each patient.

All the patients received cytarabine and an anthracycline drug to induce remission plus additional chemotherapy in an attempt to keep the cancer from returning.

Using technology developed at the Genome Institute, the researchers isolated the DNA segments that contained every mutation in the samples of cancer cells and sequenced those regions nearly 600 times each, far more than the usual 30 times each, which substantially increased the statistical accuracy of the results.

The researchers found that the relapsed cancer cells did not contain a large number of new mutations, as some had predicted. In fact, while the relapsed cells in all the patients had gained some mutations, the percentage was relatively small compared to the number of mutations in the primary tumour.

The study has been recently published in the advance online edition of Nature.
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