Personalized Medicine vs. Advanced Cancer - Molecular Profiling Extends Lives of Cancer Patients When Other Treatments Fail

April 21, 2009 (Denver) -- A personalized approach to therapy is extending the lives of some people with advanced cancer who failed to benefit from standard drug treatments.

Using molecular profiling, “we were able to predict which drug would best help a patient based on a tumor’s characteristics,” says Daniel Von Hoff, MD, senior investigator at the nonprofit Translational Genomics Research Institute in Phoenix.

“This approach can help people [whose cancer has progressed] on everything else,” he tells WebMD.

The study involved 66 patients who had failed to respond to between two and 13 different drugs for a variety of advanced cancers, including breast, colon, andprostate cancers.

“Normally, we would have to consider using an experimental therapy. But using fairly standard molecular techniques, we were able to find a conventional target for conventional drugs.

“For a breast cancer patient with estrogen receptor-positive cancer, for example, we could use an estrogen-receptor [blocker such as tamoxifen],” Von Hoff says.

In 18 (27%) of the patients, the personalized treatment delayed cancer progression, compared with previous treatments. These patients lived an average of 10 months, compared with five months for the entire study group.

The greatest benefits were seen in the 18 patients with breast cancer.

The findings were presented at the annual meeting of the American Association for Cancer Research.

Personalized Medicine Catching On

“With this trial, we are showing the power of personalized medicine, using the tools we already have available to us” Von Hoff says.

The idea of using molecular markers to personalize treatment is catching on, says Michael Caligiuri, MD, chairman of the committee that chose which studies to highlight at the meeting and CEO of the Comprehensive Cancer Center - James Cancer Hospital at Ohio State University.

At Massachusetts General Hospital in Boston, for example, the tumors of almost all cancer patients are being analyzed for genetic mutations.

The molecular pathology lab, which opened in March, “is intended to give more information about an individual patient’s cancer, so they can treat it in a very specific way, thereby significantly increasing the odds of success,” says lab co-director John Iafrate, MD.

Targeted Therapy vs. Pancreatic Cancer

Also at the meeting, Mayo Clinic researchers reported that a combination of two targeted therapies can kill pancreatic cancer cells in the lab, opening up the possibility of a new approach to treating the deadly disease.

An estimated 38,000 people in the U.S. were diagnosed with pancreatic cancer in 2008, according to the American Cancer Society. About 34,000 Americans died of the disease, making it the fourth deadliest cancer.

By the time the cancer is diagnosed, “there are few surgical options,” says Mamta Gupta, PhD. A commonly used drug is Gemzar, which extends life by five to six months, she says.

In an attempt to find a better treatment, Gupta and colleagues treated pancreatic cancer cells with a combination of two drugs: an mTOR inhibitor called rapamycin and a histone deacetylase inhibitor called LBH589.

The two drugs together killed about seven times more cancer cells than either drug alone, she tells WebMD.

Targeting Pancreatic Cancer’s Roots

Still, other researchers reported that combination drug treatment can slash the number of pancreatic cancer stem cells in mice, curbing tumor growth.

The findings are in line with the latest theory of what causes cancer, namely that stem cells hiding within tumors drive their growth. Conventional treatments fail to cure cancer, according to the theory, because they are targeting the wrong cells.

Rajesh Kumar NV, PhD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, and colleagues studied mice implanted with human pancreatic tumors.

The mice received gemcitabine (Gemzar), the most common drug treatment for pancreatic cancer; the experimental drug tigatuzumab, which induces cell death; or a combination of the two agents.

Treatment with gemcitabine and tigatuzumab provided a better punch than either drug alone, NV tells WebMD.

Treatment with gemcitabine alone reduced tumor size, but the tumor cells that remained were rich in pancreatic cancer stem cells, he says. In nearly all cases, the tumors returned.

The combo treatment, on the other hand, reduced the number of pancreatic cancer stem cells, caused tumor remission, and significantly increased the time to cancer progression, NV says.

Targeting cancer-sustaining pancreatic cancer stem cells is of paramount significance since there are few effective therapies for pancreatic cancer and most of the patients die within the first year of diagnosis, Kumar says.