Oncologist Not Afraid of the Term “Cure”
.jpg "John Marshall, MD, Chief of the Division of Hematology/Oncology")
.jpg "Dr. Marshall, along with other members of the Gastrointestinal Oncology Clinic")
John Marshall, MD, uses evolving notions of battlefield strategy when he talks about why the treatment of cancer must change.
When former President Richard Nixon declared war on cancer in the 1970s, “all we had to fight with was some antiquated, World War I technology such as nitrogen mustard, the toxic chemotherapy derived from the same compounds that make mustard gas,” says Marshall, Chief of the Division of Hematology/Oncology at the Lombardi Comprehensive Cancer Center.
“And just like chemical warfare used against those adversaries, chemotherapy affects everything it comes into contact with, be it cancerous or healthy cells, or even tumors that won’t respond to these agents,” he says. “It did work to kill some cancers such as childhood leukemia, but it has not resulted in a cure of the common adenocarcinoma cancers – breast, colon, prostate, and lung cancers.”
The problem, Marshall says, is that tumors have largely been treated based on how they appear to a pathologist and where they are located. “It’s the same kind of logic that you see in older warfare, when anyone at a particular location was viewed as the enemy.”
With the recent development of targeted therapies, however, the battle against cancer has come to resemble the military’s “war on terror,” says Marshall, a clinician who is viewed as a global leader in the research and development of drugs to treat colon cancer and other gastrointestinal (GI) cancers.
“Now individuals within a population are profiled to see if they pose a danger, and we are doing the same in cancer. Now we can profile the genetic nature of these cancers and go after them individually,” says Marshall.
But even in this era of emerging targeted treatments, Marshall maintains that the war on cancer is not being won, and that too many oncologists are content to settle for short-term success.
“The field is accepting and valuing minor improvements in survival. If a patient gets to live two weeks longer, that is viewed as a success. If they live two months longer, that is seen as a great victory,” Marshall says.
“I don’t see it that way. Treating cancer as if it is a chronic disease is problematic because those therapies inevitably result in side effects to patients and a great cost to society,” he says.
“I am not content with a prolonged battle with cancer. I want a cure - something that very few people talk about these days,” Marshall says. “I think we have lost our way.”
That is why Marshall is pulling together specialists at GUMC and the Lombardi Comprehensive Cancer Center to “do away with the old way of doing business and to actually realize individualized therapy.”
Treating GI Cancers Differently
For starters, colon cancer patients being seen at Lombardi are now being treated differently than are many similar patients around the nation, he says.
In the same way that it has been known for a number of years that breast cancer comes in three major “flavors,” recent studies have shown that there are different subtypes of colon cancer. “We now know of two but there may be as many as four,” Marshall says.
One subtype consists of 30-40 percent of colon tumors that have a mutation in a gene known as KRAS, which helps control cell growth. Patients without this mutation are much more likely to benefit from targeted therapies such as Erbitux, which is an EGFR inhibitor.
Another subtype is the 20 percent of colon tumors that express so-called microsatellite instability (MSI), a condition caused by damaged DNA that cannot be sufficiently repaired. This leads to inactivation of the tumor suppressor genes that keep cell growth in check. “We know that chemotherapy doesn’t work well in these tumors,” Marshall says.
“These two genetic profiles alone help us guide treatment in about half of all colon cancer patients,” he says.
“Everybody talks about profiling colon tumors for KRAS and MSI, but not that many people are doing it,” Marshall says. “But that is only the start for us.”
Clinicians and researchers at GUMC are making plans to profile more genes in colon cancer patients and to enter that information into what’s being called the Georgetown Database of Cancer (G-DOC) at the Lombardi Comprehensive Cancer Center. This effort will help define responsiveness to therapy based on molecular traits.
At the same time, Marshall will be working with GUMC’s drug discovery program to design new agents based on colon cancer profiling and to move these drugs rapidly into clinical testing.
“The concept of merging individualized therapy with rapid drug development is really a match made in heaven,” Marshall says. “It will allow us to get back to the business of curing cancer.”
By Renee Twombly, GUMC Communications
