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Personalized Cancer Treatment

Researchers have developed a way to predict how a cancer patient's tumor is likely to behave and which of several treatments might be most effective. This discovery could lead to a much more personalized method of cancer care.   The scientists, from the Dana-Farber Cancer Institute, combined several types of data from pre- and post-treatment biopsies of breast tumors to obtain a molecular picture of how the cancer evolved as a result of chemotherapy.

 “Better understanding of tumor evolution is key to improving the design of cancer therapies and for truly individualized cancer treatment,” said Kornelia Polyak, MD, PhD, a breast cancer researcher in the Susan F. Smith Center for Women's Cancers at Dana-Farber. The model was developed by Polyak and Franziska Michor, PhD, a computational biologist at Dana-Farber.

For the study, investigators looked at 47 patients who had pre -operative chemotherapy so their tumor could be removed more easily.  As has been increasingly recognized, a tumor contains a varied mix of cancer cells and the mix is constantly changing. This is known as tumor heterogeneity.

The cells may have different sets of genes turned on and off — phenotypic heterogeneity — or have different numbers of genes and chromosomes — genetic heterogeneity.  These characteristics, and the location of different types of cells with the tumor, shape how the cancer evolves and are a factor in the patient’s outcome. In generating their predictive model, Polyak and other researchers integrated data on the genetic and other traits of large numbers of individual cells within the tumor sample along with maps of where the cells were located within the tumors.

The computer model revealed that the genetic diversity within a tumor, such as differences in how many copies of a DNA segment are present — didn’t change much in cancers that had no response or only a partial response to treatment. Tumors with less genetic diversity among their cells are more likely to completely respond to treatment than are tumors withmore genetic complexity. “In general, high genetic diversity is not a good thing,” commented Polyak. “The results show that higher diversity is making you less likely to respond to treatment.”

While the genetic diversity of tumor cells was not strongly affected by chemotherapy in patients with partial or no response to treatment, the study revealed that certain types of cells — those more likely to grow rapidly — were more likely to be eliminated, and the locations of cell populations changed. “Based on this knowledge,” said Polyak, “we could predict which tumor cells will likely be eliminated or slowed down by treatment, and how this may change the tumor overall.” She said this information might help design further treatment strategies for patients who didn’t respond well to the initial therapy.

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