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Research Highlights

Annual Report - Winter 2010


Learning from the tumors themselves

In a novel project matching drugs to molecular targets in lung cancer, investigators at M. D. Anderson are engaging in an intensive interrogation of the tumors themselves. The underlying premise of the package of clinical trials — known as Biomarker-based Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) — is to let the biology of a patient’s tumor instruct physicians how to treat that particular tumor. BATTLE I enrolled more than 300 patients and examined four treatment options against biomarkers, representing four molecular pathways that can fuel lung cancer. Combining lessons learned from BATTLE I, as well as new molecular targets and novel therapies, researchers expect to open BATTLE II in 2010.

Waun Ki Hong, M.D., professor and head, Division of Cancer Medicine

‘Accidental’ discovery reveals potentially effective weapon

A lethal disease with few treatment options, pancreatic cancer has confounded both clinicians and researchers. But a recent epidemiologic study suggests that the drug metformin, commonly prescribed to treat type 2 diabetes, may have a protective effect against it. Taking metformin reduced the chance of developing pancreatic cancer by 62% among diabetics, the study found. Further research is needed, but this finding indicates that metformin may be an effective weapon against a daunting foe.

Donghui Li, Ph.D., professor, Department of Gastrointestinal Medical Oncology

Reported in the Aug. 1, 2009, issue of Gastroenterology.

Four culprits cornered

Four suspects often found at the scene of the crime in cancer are guilty of the initiation and progression of breast cancer in mice resistant to the disease. Investigators say they have a “smoking gun” that shows it’s no coincidence three protein receptors and the enzyme that makes them are abnormally expressed in many types of cancer. The four include three lysophosphatidic acid (LPA) receptors (LPA1, LPA2 and LPA3) and the LPA-producing enzyme, autotaxin. A number of drugs are in preclinical development to target these receptors and autotaxin.

Gordon Mills, M.D., Ph.D., professor and chair, Department of Systems Biology

Reported in the June 2009 edition of Cancer Cell.

Intense chemoimmunotherapy offers hope

Could chemotherapy alone be as successful as a stem cell transplant in treating mantle cell lymphoma, a lethal version of non-Hodgkin’s lymphoma? In a study of mantle cell lymphoma patients age 65 or younger who received an intensive regimen of chemoimmunotherapy as frontline treatment, 67% are alive and 46% remain in remission at a median follow-up of eight years. With these findings, researchers believe this intense therapy without transplant is an acceptable option for these patients.

Jorge Romaguera, M.D., professor, Department of Lymphoma and Myeloma

Reported in December 2008 at the 50th annual meeting of the American Society of Hematology.

A personalized cocktail

A lymphoma vaccine, custom-made for each study patient, extended the time the disease remained in remission. Its success shows that if patients can reach minimal disease state with chemotherapy, the vaccine can come in and mop up remaining cancer cells. It’s a strategy that investigators think should work for other cancers as well.

Sattva Neelapu, M.D., assistant professor, Department of Lymphoma and Myeloma

Larry W. Kawk, M.D., Ph.D., professor and chair, Department of Lymphoma and Myeloma, inventor of vaccine

Reported in May 2009 at the annual meeting of the American Society of Clinical Oncology.

Tricks of brain metastases

Cancer that spreads to other organs finds a particularly inviting hideout in the brain, where it is usually far harder to treat than in other locations. Research now shows that brain metastases exploit spider-like cells called astrocytes into protecting the tumor cells from therapy. Astrocytes normally play the important role of providing oxygen and nutrients to neurons. When subverted, they are an important factor in a tumor’s resistance to chemotherapy. Therapy for brain metastases must target both the tumor cells and the surrounding astrocytes that contribute to their survival and growth.

Isaiah Fidler, D.V.M., Ph.D., professor, Department of Cancer Biology; director, Cancer Metastasis Research Center

Raymond Sawaya, M.D., professor and chair, Department of Neurosurgery

Reported in April 2009 at the 100th annual meeting of the American Association for Cancer Research.

Dramatic increase in survival

Novel chemotherapy and biological agents for metastatic colorectal cancer, combined with surgical advances in liver resection, have resulted in a dramatic increase in survival for patients with advanced disease. The first study in 20 years to examine survival in these patients found that the median overall survival is now more than 30 months, compared with eight for those diagnosed before 1990. For those diagnosed after 2004, the five-year survival is more than 30%. Such improvement is rarely seen in metastatic cancers.

Scott Kopetz, M.D., Ph.D., assistant professor, Department of Gastrointestinal Medical Oncology

Jean-Nicolas Vauthey, M.D., professor, Department of Surgical Oncology

Reported in the Aug. 1, 2009, issue of the Journal of Clinical Oncology.

Addressing a hotbed of instability

When scientists set out to understand the role of the gene Bcl 6, short for B-cell lymphoma 6, they discovered that its expression in T lymphocytes promoted the formation of germinal centers, a hotbed of genomic instability. Germinal centers not only are implicated in autoimmune diseases such as lupus and rheumatoid arthritis, but also give rise to some types of B-cell lymphoma. The scientists are setting out to investigate the mechanisms of Bcl 6 action and its roles in immune diseases and cancer.

Chen Dong, Ph.D., professor, Department of Immunology

Reported in the Aug. 21, 2009, issue of the journal Science.

Key to understanding

Often when ovarian cancer is removed, leaving no remaining sign of disease, the cancer grows back after two or three years. Researchers have now identified a single tumor-suppressing gene called ARHI that is a key to maintaining, and perhaps killing, dormant ovarian cancer cells that persist after initial treatment only to reawaken years later. The gene acts as a switch for autophagy, or self-cannibalization, in ovarian cancer cells. But researchers have discovered that in this case partial “self-eating” acts as a survival mechanism for dormant cancer cells.

Robert Bast Jr., M.D., vice president for translational research

Reported in the December 2008 Journal of Clinical Investigation.

Collaborative efforts benefit pediatric patients

A multi-institutional study led by researchers at M. D. Anderson found that using chemotherapy alone and delaying or avoiding cranial radiation altogether can be effective in treating pediatric patients with inoperable or progressive low-grade glioma. Although radiation is often effective in this most common brain tumor in children, the long-term effects can be detrimental to young patients. This study confirmed the ability of chemotherapy to control the disease.

Joann Ater, M.D., professor, Division of Pediatrics

Reported in October 2008 at the 40th annual International Society of Pediatric Oncology Meeting, Berlin, Germany.

Putting the body’s defense system to work

A vaccine for advanced melanoma, one of the most lethal cancers, showed improved response rates and progression-free survival for patients when combined with the immunotherapy drug, interleukin-2. This agent stimulates the body’s own immunologic defense system to attack tumor cells and rid the body of cancer without destroying healthy tissue.

Patrick Hwu, M.D., professor and chair, Department of Melanoma Medical Oncology

Reported in May 2009 at the annual meeting of the American Society of Clinical Oncology.

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