By Michael Claeys
As experts like to point out, cancer isn’t just one disease. And so understanding what causes the various forms of cancer and pinpointing effective treatments requires the insight and investigative skills of scientists from several disciplines.
Many of these discoveries come from the Stanford School of Medicine, where more than 300 scientists and clinicians have made cancer their focus. Below is a small sample of the Stanford findings reported during the past year that are moving cancer research forward:
Researchers have identified a compound that kills kidney cancer cells by restricting their prime energy source: glucose. In animal studies, the drug halved the amount of glucose imported by tumor cells, slowed tumor growth and produced few side effects.
If successful in humans with kidney cancer, the compound may offer an improvement over current chemotherapy drugs that indiscriminately kill cancer cells and other rapidly dividing cells, like blood and hair follicle cells.
“This study demonstrates an approach for selectively inhibiting the ability of cancer cells to take up glucose, which is a pretty powerful way of killing those cells,” says senior author Amato Giaccia, PhD, professor of radiation oncology, whose study was published in Science Translational Medicine.
People with a genetic disease called basal cell nevus syndrome develop hundreds, even thousands, of skin cancers each year. Many require frequent surgeries and develop significant scarring. A clinical trial by Jean Tang, MD, PhD, assistant professor of dermatology, found that an experimental drug significantly slowed or stopped the development of tumors in each of 24 patients who received the drug, and caused existing tumors to shrink in size. Tang presented the findings at the annual meeting of the American Association for Cancer Research.
The results were so positive that the randomized, placebo- controlled trial was halted early to allow all participants access to the drug, Genentech’s GDC-0449.
“Many of our patients enrolled in this trial not because of their own disease but for their children who have inherited the same mutation,” Tang says.
Measuring tumors’ initial response to treatment allowed researchers to predict the efficacy of a gene-targeting lung cancer treatment, they reported in Science Translational Medicine.
Some forms of cancer are highly dependent on the activity of specific cancer-causing genes called oncogenes. Dean Felsher, MD, PhD, and his colleagues observed that inhibiting oncogenes caused some tumors to shrink in a rapid and distinctive way, enabling the researchers to create a mathematical “signature” of an oncogene-dependent tumor. The formula’s accuracy was validated in a trial of an oncogene-suppressing drug. Patients with robust initial response had the predicted sustained tumor regression.
“With some simple measurements, we found we can determine when a cancer is addicted to a particular cancer gene and will respond to therapy targeting that gene,” says Felsher, associate professor of medicine and of pathology.
Leukemia patients whose cancers express higher levels of genes associated with cancer stem cells have a significantly poorer prognosis than patients with lower levels of the genes. The finding is among the first to show that the cancer stem cell hypothesis — that some cancers spring from and are replenished by a small population of hardy and self-renewing cells — can predict outcomes in a large group of patients.
The study published in the Journal of the American Medical Association was led by Ash Alizadeh, MD, PhD, assistant professor of oncology. To gather the data, he and his colleagues conducted a retrospective analysis of more than 1,000 acute myeloid leukemia patients.
“The clinical implications of this concept are huge,” says Alizadeh. “If we’re not able to design therapies to target this self-renewing population of chemotherapy-resistant cells, the patients will continue to have a tendency to relapse.”
A bioengineered protein has been shown to prevent cancer cells from creating new blood vessels, thereby restricting access to nutrients and impairing tumor growth. The protein blocks two chemical receptors that regulate new capillary creation — a process called angiogenesis. When tested in mice, the protein inhibited angiogenesis more effectively than single-receptor blockers.
“Samples treated with our dual-action protein have minimal blood vessel formation, similar to a sample in which angiogenic factors are absent,” says lead researcher Jennifer Cochran, PhD, assistant professor of bioengineering. The study was published in the Proceedings of the National Academy of Sciences.
Beyond cancer, preventing angiogenesis could help treat such diseases as macular degeneration, one form of which impairs vision through unchecked capillary growth in the retina.