Tackling Cancer from Every Angle

This colorized scanning electron micrograph (SEM) shows a cell from human breast cancer tissue.

This colorized scanning electron micrograph (SEM) shows a cell from human breast cancer tissue.

From findings on how tumors spread to the identification of new drug targets, HHMI researchers have made significant discoveries in the past year that will improve the ability to detect and treat cancer.

At the Johns Hopkins Kimmel Cancer Center, HHMI investigator Bert Vogelstein and colleagues sequenced tens of thousands of genes from patients with pancreatic cancer and glioblastoma, the most aggressive form of brain cancer. With this most detailed genetic survey yet of any human tumor, the team identified hundreds of relevant genes. In some cases, the tumor cells carried too many or too few copies of a gene. In other cases, the tumor cells had a mutated form of a gene. The average tumor cell carried more than 60 genetic alterations, some of which could be useful drug targets.

Using a different method to detect genes that cancer cells rely on for survival, independent teams led by HHMI investigators D. Gary Gilliland at Brigham and Women’s Hospital (now senior vice president at Merck Research Laboratories) and Stephen J. Elledge at Harvard Medical School discovered other weak spots in cancers. The researchers used RNA interference (RNAi) technology to turn off genes in cancer cells and see which ones affected the cancer’s survival.

Although methods such as these can identify single genes involved in tumor formation, some cancers are caused when chromosomes swap pieces of genetic material, causing two otherwise normal genes to fuse. This year, HHMI investigator Arul Chinnaiyan at the University of Michigan Medical School developed a new technique to pinpoint such cancer-causing fusion genes. He showed the strength of the technique by using it to detect the so-called Philadelphia chromosome—a chromosome swap known to cause a fusion gene that leads to chronic myelogenous leukemia—as well as fusion genes linked to prostate cancer.

Tumors are often their deadliest when they metastasize, and two HHMI investigators this year identified genes linked to this process. Joan Massagué of Memorial Sloan-Kettering Cancer Center implanted tumor cells from advanced breast cancer into mice and then isolated tumor cells from mice whose cancer spread to the brain. They found 243 genes with unusual expression patterns and narrowed their focus to 17 genes that help breast cancers spread to the brain. Michael Green at the University of Massachusetts Medical School looked at metastasis from a different angle. His lab used a genetic screen to find 22 genes that, when blocked, allow tumors to spread.

On the treatment side, investigator Charles L. Sawyers of Memorial-Sloan Kettering Cancer Center unveiled a new therapy for prostate cancer. Sawyers developed the drug MDV3100 to combat prostate tumors resistant to current therapies. In early clinical trials, the drug decreased PSA levels, one marker of prostate cancer, in 22 of the 30 men enrolled. It is now being studied in a phase III clinical trial that will determine its overall effectiveness in a broad population of patients.

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Image credit: NIH