By Allison Proffitt
August 10, 2009 | Researchers at MIT have found that the genetic profiling of tumors can help doctors choose which type of chemotherapy to use. “This is a concrete example of how systems biology can impact patient care,” Michael Yaffe, an MIT biology professor, told Bio-IT World.
Yaffe and Michael Hemann led the study. Both are biology professors and members of the David. H. Koch Institute for Integrative Cancer Research at MIT (see, MIT Launches Interdisciplinary Cancer Center). The work will be reported in the Aug 15 issue of Genes and Development.
The research team focused on p53 and ATM, two proteins active in cancer that have long been known to play some role in a cancer’s response to chemotherapy. P53 is a tumor suppressor gene that activates repair systems when DNA is damaged and induces apoptosis when damage if irreparable. ATM is known to help regulate p53 and is involved in controlling the cell’s response to DNA damage. Mutations in one or both are often seen in tumor cells.
The new study shows that when both p53 and ATM are abnormal, tumors are highly susceptible to DNA-damaging chemotherapy. Tumors in which ATM is mutated but p53 is not, are highly resistant to chemotherapy. Tumors in which p53 is mutated but ATM is not seem to be less responsive to chemotherapy.
“This is a case where two common markers, when taken together, were very predictive,” said Yaffe. “It didn’t come from looking at patients it came from very basic research.”
Yaffe stresses that this is a solution that is applicable immediately. “You could use this today,” he says. “You do immunohistochemistry for the tumor, for p53 and ATM, and based on [the results] you can choose anthrocyclines [if appropriate], or taxol as an alternative based on this data.”
The team focused on breast cancer. “We know that this works in breast cancer, we haven’t explored it in other cancers… It would probably be true in other tumors as well,” said Yaffe.
The results also suggest alternative treatment pathways either by inhibiting ATM, or targeting other DNA repair proteins to increase the tumor’s susceptibility to chemotherapy.