January 23, 2012

Creativity fuels ideas for cancer cures

Historic Hurd Hall on Johns Hopkins’ East Baltimore campus was filled to capacity on Jan. 13 with students, faculty and staff waiting to hear five scientists—all in the early part of their careers—describe their novel ideas on how to cure metastatic cancer. The five were finalists, chosen from among 44 entrants, in a competition on creative thinking named for John Rangos Sr., chairman of the Rangos Family Foundation, who funded the awards. Each scientist had 10 minutes to present his or her idea and answer questions from a panel of faculty judges, who would select the winners based on the novelty and scientific merit of their ideas, as well as the feasibility of future clinical applications of their proposals.

Donald Coffey, whose theory on killing cancer by weakening its DNA scaffolding continues to spur innovative research, opened the event, describing it as the “Olympics” of research competitions at Johns Hopkins.

The finalists were awarded the John G. Rangos Medal of Honor in Creative Thinking, and the top three received cash prizes: $20,000 for top-place winner Andrew Sharabi, $5,000 for second-place winner Cheng Ran “Lisa” Huang and $1,000 for third-place winner Diane Heiser.

This is the first year of the program, which has the goal of encouraging young people to look at the problem of metastatic cancer, propose new research strategies and be given a chance to pursue their proposals.

“Every family knows someone who has suffered from cancer. Some forms of the disease, such as testicular cancer, are curable even after they have spread, but most are not,” Rangos said earlier. “This competition has solicited ideas from the minds of bright young students with creative approaches to solving the dilemma of metastatic cancer, and I am extremely honored to be part of it.”

The competition was open to all currently enrolled full-time students and trainees at The Johns Hopkins University, including undergraduate, graduate and medical students; residents; and fellows.

Rangos, who has had a long association with Johns Hopkins Medicine, worked with faculty members in the Department of Urology, including Coffey and Horst Schirmer, to develop the program.

Organizers plan to continue the competition in future years and perhaps open it up to students at other institutions.

“Why some metastatic cancers can be cured while most cannot is one of the most provocative questions in medicine,” Coffey said, “and it will take novel, creative approaches to overcome this very difficult challenge.”

First up to the podium was medical oncology fellow and eventual fifth-place winner Kevin Cheung, who proposes turning back the clock on cancer cells by reprogramming them into germ cells. He suggests that the reason testicular and other germ cell tumors have high cure rates is because of their undifferentiated state. Just as scientists have created immature pluripotent stem cells from adult cells, Cheung says that the same could be done with cancer cells. By age reversing resistant cancer cells, he proposes to make them sensitive to conventional chemotherapy.

Third-place winner Diane Heiser, a doctoral candidate in Cellular and Molecular Medicine, proposes that more metastatic cancers can be cured by understanding how cancer cells repair their own DNA. She suggests that metastatic cancer cells are able to survive the severe DNA breaks that occur with DNA damaging agents like chemotherapy, by repairing themselves quickly and efficiently, and says that determining the specific proteins that help metastatic cancer cells repair their DNA could reveal new targets for drugs that sensitize cancer cells to chemo or radiation therapy.

Genetics postgraduate student and second-place winner Huang describes cancer as a “fight between two parasites: cancer vs. transposons.” She notes that nearly half of the human genome is made up of “jumping” DNA, short sequences of DNA that get inserted into the genome at various points; too many transposons can lead to genomic instability and kill the cell. Huang says that germ cell tumors have the highest level of transposon activity, making them more prone to cell death and, thus, more easily killed by chemotherapy drugs.  There is potential, she says, of using drugs to target proteins that normally suppress transposon activity in most cell types.

Brian Ladle, a pediatric oncology fellow and fourth-place winner, posits that cancer cure rates depend on the cancer cells’ level of uniformity. Low-risk pediatric leukemias are mostly curable, he says, and most of the cells have uniform qualities and certain genetic abnormalities in common. Cancers that are more difficult to cure are less uniform. Ladle suggests that targeting different populations of cells within cancers could result in fewer relapses and more cures.

The overall prize went to radiation oncology resident Sharabi for his idea titled “Specific Immune Response Against Testicular Cancer: A Proposed Mechanism for Long-Term Remission.”

Sharabi suggests that metastatic testicular cancer is largely curable in most patients because immune cells zero in on testicular cancer cells with far more accuracy than they do in other cancers. He proposes that testicular cells are essentially recognized as foreign to the immune system because the testes are protected by the so-called blood-testis barrier, much like the blood-brain barrier. Testicular cancer cells can spread to the rest of the body and may initially go undetected by immune system cells. However, he says he believes that chemotherapy given to patients causes testicular cancer cells to die, releasing many targets for the immune cells. At that time, the immune system kicks into high gear, generating large numbers of circulating immune cells, whose task is to seek the testicular cancer cells and destroy them. He also believes that after chemotherapy, testicular cancer cells essentially may be recognized as foreign by the immune cells because the blood-testis barrier had, until then, kept testicular cells hidden from the immune system.

He proposes further investigations of how the immune system responds to testicular cancer cells to identify specific immune system targets common to testicular cancer as well as other types of cancer. The research could lead to the development of vaccines that prime the body to defend against and fight cancers.

Just before Sharabi was announced the top winner, Rangos called Johns Hopkins a “beacon of light in the measurement of medicine.” It is here, he said, that we’ll find the next generation of scientific leaders.