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‘Avatar’ mice help develop new cancer treatments

Boston medical center, Maine lab team up in a new project: implanting rodents with a patients’ actual cancers to be able to fight them better

Mice are being developed that can be implanted with human cancer cells, allowing for drug tests on those human cells.
Aram Boghosian/Boston Globe
Mice are being developed that can be implanted with human cancer cells, allowing for drug tests on those human cells.

Some of the most important occupants of Beth Israel Deaconess Medical Center live in cages in a gleaming tower near Longwood Avenue. They are furry little mice, in varieties of white and brown and black, with long pink tails. And they could play a vital role in the search for cures for cancer.

Beth Israel Deaconess has been studying cancer in the thousands of rodents housed in its facilities, and now the medical center is poised to expand that research, using a new type of lab mouse that can host human cancer cells. The goal is to help scientists develop a custom treatment for each patient’s form of cancer.

Beth Israel Deaconess has formed a new partnership with Jackson Laboratory, a nonprofit research center in Bar Harbor, Maine, that is one of the largest suppliers of mice for medical research. Jackson produces 3 million mice a year and distributes them to labs around the world, where scientists use them to learn more about disease in humans.

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One of the newer achievements at Jackson is the development of a mouse that can be implanted with cells from a human cancer and grow the same cancer as the human patient. By testing drugs on the mouse, scientists can learn how the human patient will respond to those drugs. This method allows researchers to hone in on an individual’s cancer and its genetic uniqueness, rather than a general type of cancer.

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“Our mouse models are actually human tumors growing in mice,” said Dr. Edison Liu, Jackson’s chief executive.

This approach is different from the one employed by scientists at Beth Israel Deaconess, in which they alter the genetic makeup of mice. By inserting or deleting certain genes, they engineer a mouse to develop a certain cancer.

By combining these approaches, scientists at Jackson and Beth Israel Deaconess believe they will have a better understanding of how cancer progresses and how drugs can stop it from spreading.

“You put these two together, and you have a really powerful platform,” Liu said. “Not only can you empirically test if something works or not, you can figure out why it doesn’t work.”

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The partnership is the first of its kind for the two institutions. Scientists will team up on clinical research and on developing better ways to diagnose cancer by analyzing the DNA of an individual patient’s tumors.

Beth Israel Deaconess treats about 10,000 patients a year at its cancer center.

The institutions also plan to develop a curriculum to help teach doctors about advances in cancer and genetics. At big research centers, doctors are studying the genetic intricacies of cancer, but doctors in community hospitals and clinics are generally unaware of new technologies and diagnostics, said Dr. Jeffrey E. Saffitz, the chairman of pathology at Beth Israel Deaconess.

“The whole concept of genomics is advancing very rapidly,” Saffitz said, “but most doctors are mostly ignorant of this.”

Mice have long been used in medical research. Scientists have learned how to give mice diseases, then try to cure them, hoping that what they see in mice will help them treat humans.

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Rodents typically are used to test experimental drugs before the drugs are given to humans. But a few years ago, Dr. Pier Paolo Pandolfi, director of the Beth Israel Deaconess cancer center, began a different approach: testing drugs in mice and humans at the same time. Such trials allow researchers to speed up drug testing.

Dr. John Clohessy holds a mouse that has cancerous prostate cells; a microscope slide (above) of a cancerous mouse prostate.
The Boston Globe
Dr. John Clohessy holds a mouse that has cancerous prostate cells; a microscope slide (above) of a cancerous mouse prostate.

Pandolfi said he wants to extend this approach so that each human patient is paired with two mice: one genetically modified to develop cancer, and one implanted with the human patient’s cancer — called a mouse avatar.

Each mouse model provides scientists with different information about how a disease progresses and responds to drugs.

“With Jackson, we’ll align the two operations,” Pandolfi said. “We’ll scale up.”

Beth Israel Deaconess has started experimenting with the avatar approach for a handful of patients with cancers of the prostate, pancreas, breast, and adrenal gland. The concept is still in the early stages, but it is drawing interest. Several cancer patients from outside of Boston have learned of Pandolfi’s work and have even shipped him their tumor cells so he can create their mouse surrogates. By experimenting on the avatar, Pandolfi and his staff can determine which drugs might work best for that patient.

Implanting cancer into a mouse and testing drugs on the mouse can take many months — too long for patients with advanced cancer. But avatars could help patients with less aggressive forms of the disease.

The cost of creating an avatar starts at about $3,000, but testing drugs in the avatar costs much more. Beth Israel Deaconess uses grants to cover these costs now, so that patients do not pay out of pocket. Pandolfi said he hopes insurance companies will eventually pay for this approach.

A microscope slide of a cancerous mouse prostate.
Aram Boghosian/Boston Globe
A microscope slide of a cancerous mouse prostate.

Mouse science has its critics, including animal rights activists and research specialists who believe that mice in general are poor predictors of how humans will respond to diseases and medications.

But the National Cancer Institute is encouraging scientists to continue rodent research and to use different types of mice, as Beth Israel Deaconess is doing.

“We believe that if we’re going to improve the reliability of information from animal models that we’re going to have to use a variety of models,” said Cheryl Marks, associate director of the division of cancer biology at the National Cancer Institute, near Washington, D.C.

“We seem to need every tool in the shed.”

Priyanka Dayal McCluskey can be reached at priyanka.mccluskey
@globe.com
. Follow her on Twitter @priyanka_dayal.