Fordham Alum Discusses Cancer Treatment Research

Studies of the Evolution of Cancer in the Cells of Mice Give Clues to Treating the Disease in Humans

By LAURA CHANG

Published: December 11, 2008

On Dec. 4, Fordham College at Lincoln Center’s (FCLC) Science Club hosted a Lawless Series Speaker, Cory Abate-Shen, Ph.D.  Each Lawless speaker is invited for his or her important work and for the purpose of helping “to expose new students to the sciences,” said Mohammad Usmani, FCLC ’10 and president of the Science Club.  Abate-Shen, a Summa Cum Laude at Fordham, informed over 30 FCLC students and faculty about her studies with cancer research in mice.

Abate-Shen discussed her experiences with Rev. Lawless, for whom the series is named, when he served as one of her mentors during her studies at Fordham.

“Mentors guide us without force and help find your way, not the way,” Abate-Shen said. It was “the influences that came together” that ultimately inspired Abate-Shen to follow her passion in science, she said.

After obtaining her B.A. in psychology at Fordham University, Abate-Shen attended graduate school at Cornell University Medical College. She is a professor of urology and pathology at Columbia University College of Physicians and Surgeons and is the associate director of the Herbert Irving Comprehensive Cancer Center.

Abate-Shen explained how studying cancer mechanism in mice assisted the understanding of cancer in humans. She said, “In my laboratory, we use genetically engineered mouse models to literally give mice cancer, and then we try to see if we can use those mice to understand how cancer evolves and whether we can develop new treatments.” Mice with cancer share a lot of similarities with humans with cancer, Abate-Shen said. She continued, “What we really want to do is tackle all of the stages of cancer…Mice allow you to interrogate the pathway of cancer.”

One of the major cancers studied at her lab is prostate cancer, Abate-Shen said. She said that it is a very common cancer and has many features that exemplify how cancer evolves.  Cancer evolves from normal cells, then progresses into pre-evasive cells—which means that the cancer has formed but remains within the capsule and is still pre-malignant—until finally it reaches the cancerous stage where the cells escape from the capsule. It is at the metastasis stage when cancer is most serious and not treatable, thus Abate-Shen explains, “We want to slow down the process…find it, protect it early on, before it reaches metastasis.”  By using mice, she is able to examine cancer at all of the stages.  A pivotal hormone, Androgen, is required for this entire process to occur, but once it is removed, the cancer, which is “amazingly dependent upon the hormone,” will find a way to overcome it, Abate-Shen said. “Androgens are critical.”

In a treatment study, mice that were androgen-deprived resulted in the initial temporary disappearance of cancer, Abate-Shen said; however, the cancer reemerged, in sometimes less than a year, in a form that was no longer dependent on a source of androgens but rather “is really, really aggressive,” she said. Therefore, the treatment only delays the cancer; it does not treat it.

With the mouse model, Abate-Shen was able to discover the signaling pathways of cell proliferation.  There were two pathways discovered, AKT and MAP kinase, which help promote cancer progression.

“By inhibiting the pathways, you can inhibit the growth,” she said. Engineered cancer cells were placed in these mouse models, which helped develop current therapies. In order to inhibit the signaling pathways, Abate-Shen said, you need two drugs, each to treat the two pathways, and then you have to be able to use them together—in this case Rapamycin and PD0325901—Abate-Shen said.  The drugs need to get into the mice and get to pathways they are supposed to inhibit, she explained.

Abate-Shen said that, in Androgen-deprived mice, “the cancer was stripped almost down to nothing.”

“When choosing drugs, we choose drugs that we can actually give patients.” She said Rapamycin is a very common drug that is used.  Upon discovering this in mice, Abate-Shen said the next step was to try it in humans. She collaborated with pathologists to sample prostate cancer patients in order to find out if they had both pathways activated.

She said that she discovered that 25 percent of those patients had both pathways activated.  “You can imagine a large percentage of patients could benefit from these agents [Rapamycin and PD0325901],” Abate-Shen said.

Lillian Chiu, FCLC ’11, a psychology major, said that she found the discovery of the two drugs to be “the most interesting” part of the presentation and said she felt that it “provided good research opportunities.”

At the end of the forum, Usmani said that after attending several of these forums, “It is the same problem that can be looked at in different ways, but [all the forums and research] shares the same goal, and that is to cure cancer.”