Last Friday, the historic Hurd Hall at Johns Hopkins was filled to capacity 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. It was part of a competition on creative thinking named for John Rangos Sr., chairman of the Rangos Family Foundation, who funded the awards. Rangos worked with Johns Hopkins faculty members Donald S. Coffey and Horst Schirmer in the Department of Urology to develop the competition.
Each scientist had 10 minutes to present their idea and answer questions from a panel of Johns Hopkins faculty judges.
Master of creative thinking, 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 winners received cash prizes.
First up to the podium was medical oncology fellow and fifth place winner Kevin Cheung who proposed turning back the clock on cancer cells, reprogramming them into germ cells. He suggested 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, proposed 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. Heiser says that determining the specific proteins which 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 Cheng Ran "Lisa" Huang described cancer as a “fight between two parasites – cancer versus transposons.” She noted 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, presented his idea that cancer cures rates depend on the level of uniformity between cancer cells. 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 Andrew Sharabi for his idea entitled “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 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, when patients receive chemotherapy, he believes that this 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. Sharabi believes that after chemotherapy, testicular cancer cells may be essentially recognized as foreign by the immune cells because the blood-testis barrier had, until then, kept testicular cells hidden from the immune system.
Sharabi 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 development of vaccines that prime the body to defend against and fight cancers.
Just before Sharabi was announced the top winner, John Rangos Sr. called 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.
Congratulations to the Rangos award finalists and all those who value creativity and innovation.