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Influx of Funding Impels Collaborative Explorations to Study Sarcoma as Behavior Model for Other Cancers

Influx of Funding Impels Collaborative Explorations to Study Sarcoma as Behavior Model for Other Cancers

ABSTRACT: This rare cancer finally sheds its FDA designation as an orphan disease.
FDG-PET/CT fusion image of the legs
FDG-PET/CT fusion image of the legs, frontal section, showing liposarcoma of the left thigh. Liposarcoma is a malignant tumor that develops in deep soft fatty tissue.

Sarcoma accounts for just 1% of all cancers in the U.S. annually, so its designation by the FDA as an orphan disease is not surprising. Despite its rarity, these bone tumors have emerged as an important model for how more common cancers behave. In fact, drugs in development for sarcoma treatment are proving to be effective in ovarian, lung, and breast cancer. This orphan disease is finding a home in the cancer care continuum and experts told Oncology News International that there has never been a better time to be engaged in sarcoma research.

"The U.S. government has identified sarcoma as one of the diseases they are going to help, over the next several years, to find ways to treat and ways, hopefully, to cure," said Gary K. Schwartz, MD, chief of the Melanoma & Sarcoma Service at Memorial Sloan- Kettering Cancer Center (MSKCC) in New York. Dr. Schwartz's lab is currently working with grants from NCI and the American Recovery & Reinvestment Act (ARRA) to learn more about the molecular pathways of the disease.

"I would say there is a great deal of hope," said Lee Cranmer, MD, PhD. "Sarcomas are very tough nuts to crack, but we are making progress. Future generations—and I don't mean many generations, I mean the next generation—will not have the same burden of this problem as we experience now." Dr. Cranmer is an associate professor of clinical medicine at the Arizona Cancer Center, University of Arizona in Tucson.

GARY K. SCHWARTZ, MD
GARY K. SCHWARTZ, MD

Oncology News International spoke with sarcoma specialists for an update on the current treatment options and what the future holds.

Genetic blueprint

Chemotherapy, radiotherapy, and surgery have been the primary treatment modes for sarcoma. Researchers have begun to look at the molecular biology of the different sarcoma subtypes in order to pin down targets that can be inhibited with drugs.

"That's the tack we've been taking for the last two or three years, to really dissect the sarcoma cell and begin to see the proteins and the pathways that are critical for those sarcoma cells to survive and find ways to block or interrupt those pathways with new small-molecule, targeted agents," said Dr. Schwartz, who is also a professor of medicine at Weill Cornell Medical College in New York.

LEE CRANMER, MD, PHD
LEE CRANMER, MD, PHD

With the NCI and ARRA funding, Dr. Schwartz and colleagues at the MSKCC Laboratory of New Drug Development are conducting studies on an antibody that blocks the insulin-like growth factor receptor (IGF-1R) that is commonly found in sarcoma cells. The antibody is being studied in combination with the mTOR inhibitor temserolimus (Torisel). "Other studies are being planned that will target the sonic hedgehog pathway and the notch pathway in patients with metastatic sarcoma," Dr. Schwartz said.

Researchers have begun to do gene arrays and DNA examinations to discover the actual genes unique to each sarcoma subtype. "We have to look at each subtype, and then at the specific genes, and then discover if there is a drug that can block those genes—and do this for every specific sarcoma subtype. That's the next step in refining sarcoma research, and those studies are just about to begin," Dr. Schwartz added.

JONATHAN TRENT, MD
JONATHAN TRENT, MD

About half of sarcomas are caused by specific, well-defined genetic events, such as a mutation or deletion or amplification, explained Jonathan Trent, MD, an associate professor at Houston's M.D. Anderson Cancer Center. "We are finding now that each different sarcoma is caused by a specific genetic event, and treatment of those specific tumors has to be individualized to the specific histology. This highlights the importance of getting a sarcoma patient's genetic blueprint."

"If there is one gene that is causing this cancer, surely we can develop therapies to target these genes. We can develop a therapy to target the gene that causes the cancer and then we stand a good chance of helping a lot of people. That is a very attractive prospect to me," he added.

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