Recently in Clinical Cancer Research Category

By Laura Sussman

MET protein levels correlate strongly with a cellular transition that occurs in a treatment-resistant type of colorectal cancer, according to new research from The University of Texas MD Anderson Cancer Center.

The study results, which compared MET protein expression with protein/gene expression of epithelial to mesenchymal transition (EMT) markers and evaluated impact on survival, were released today at the annual meeting of the American Society of Clinical Oncology in Chicago.

"When the epithelial cells that line the colon become cancerous, some of them develop special features to allow migration, causing the cancer to be more aggressive," says Kanwal Pratap Singh Raghav, M.D., fellow in MD Anderson's Division of Cancer Medicine. This transition from immobile epithelial cells to mobile mesenchymal cells is associated with cell migration and invasion, treatment resistance and metastasis.

"Although EMT is a dominant molecular subtype, a biomarker suitable for clinical use has not been found. This research gives us an important step toward learning more about treating this colorectal cancer subtype," Raghav says.

The study takes another step toward personalized cancer diagnosis and treatment.

"While we know there are many of types of colorectal cancer, we're not as advanced as we'd like to be in our understanding of them," says Scott Kopetz, M.D., Ph.D., associate professor in MD Anderson's Department of Gastrointestinal Medical Oncology and senior author of the study. "One of the larger goals of our research is to classify simple biomarkers that can be used by doctors in the community to identify subtypes. We want to condense sophisticated gene signatures down to single markers and simple tests that can be used to guide therapy."

By Will Fitzgerald

In a large national, cooperative trial led by MD Anderson, researchers determined bevacizumab (Avastin), did not offer survival benefit to patients with newly-diagnosed glioblastoma. 

The most common and deadly form of brain tumors, glioblastoma afflicts more than 22,000 people each year.  Bevacizumab is currently approved in second-line treatment for patients with recurrent disease.

As a complement to the survival study, two related MD Anderson studies are shedding light on the quality of life and cognitive function of brain cancer patients receiving bevacizumab in the front-line setting.

Jeffrey Wefel, Ph.D., associate professor in MD Anderson's Department of Neuro-Oncology, says it's hypothesized that bevacizumab may affect the radiographic characteristics of a brain scan making it difficult to see tumor progression.

As a result, the study sought to determine whether radiographic improvement correlated with improvement in neurocognitive function.

By Laura Sussman

Following surgery, radiation and chemotherapy with a drug that hinders formation of tumor-supporting blood vessels does not increase the survival of glioblastoma patients, according to a phase III clinical trial.

Results of the first randomized, double-blind clinical trial of the drug bevacizumab (Avastin) for newly diagnosed glioblastoma patients were presented at the American Society of Clinical Oncology 2013 Annual Meeting in Chicago by Mark Gilbert, M.D., professor in MD Anderson's Department of Neuro-Oncology.  

Glioblastoma is the most common and lethal form of brain cancer. More than 12,000 people will be diagnosed with the disease in 2013, with an average survival rate of less than 18 months, Gilbert says.  

Bevacizumab is a monoclonal antibody that blocks vascular endothelial growth factor-A (VEGF-A), which is produced by glioblastoma to stimulate blood vessel growth.

"Glioblastoma is a cancer with too few effective therapies," said Gilbert, who also holds the Blanche Bender Professorship in Cancer Research. "When we launched this study, those in the field of brain cancer - both the scientific and patient communities -- were excited. Bevacizumab recently received approval in the second-line (recurrent disease) setting, and we knew some physicians were already giving the drug as a frontline therapy -- even with virtually no data to support that decision. It was important from a patient care and regulatory standpoint that we conduct this trial."

  MD Anderson scientists Jim Allison and Hagop Kantarjian, at left, and Guillermina Lozano and Gabriel Hortobagyi, at right, won four of 14 individual awards for senior scientists at the AAACR Annual Meeting 2013 in Washington, D.C.

Highlights

Scientists and clinicians from across MD Anderson presented their latest research findings at the AACR Annual Meeting 2013 in Washington, D.C. 

A record six scientists, from post-doctoral fellows to junior faculty to senior investigators, won awards at the meeting run by the American Association for Cancer Research, the oldest and largest organization dedicated to cancer research in the world.

By the numbers, MD Anderson faculty members, post-docs and graduate students presented (follow link to Advanced Search, type MD Anderson in institution box):

• 160 research posters in 152 poster sessions.
• 25 oral presentations or invited talks
• 10 educational sessions
• 4 lectures tied to major awards.

Highlighted work included research by Xifeng Wu, M.D., Ph.D., professor and chair of the Department of Epidemiology, showing that low bilirubin levels in the blood are a sign of high risk for lung cancer among male smokers.

Elsa Flores, Ph.D., associate professor in the Department of Biochemistry and Molecular Biology, Her presentations included one that shows p63 and p73 can provide back-up tumor suppression when their more famous sibling, p53, is inactivated.  However, they also need to be protected from themselves or they might shut down all three tumor-blocking genes.

Ellen Gritz, Ph.D., chair and professor of the Department of Behavioral Sciences, co-authored a new AACR statement urging physicians to more closely monitor their patients' tobacco use and to provide smoking cessation information during clinical visits. 

By William Fitzgerald

Gordon Mills, M.D., Ph.D., recalls a proposal he wrote 18 years ago detailing the concept of personalized cancer therapy and its potential impact. Today, that idea is no longer a proposal, but a reality, and it's about to get a boost.

Under a new and innovative institutional protocol called Clearing House, which started in March 2012, scientists are delving deeper into the biology of patients' tumors, with hopes of identifying specific genetic markers and prescribing therapies to attack those markers directly.

Funda Meric-Bernstam, M.D., professor in MD Anderson's Department of Surgical Oncology, and Mills, professor and chair of the institution's Department of Systems Biology, are leading the effort that will test up to 200 genes known to influence cancer in patients with aggressive or recurring disease.

"In the first year, we'll have sequenced the genes of far more than 1,000 MD Anderson patients and are targeting to have more than 3,000 by the second year," Meric-Bernstam says. "This will accelerate our discovery approaches, and we can develop new clinical trials, in which we already have patients pre-identified to enroll."

While the research began with solid tumors, the Clearing House protocol has expanded to all diseases that have ongoing genomically selected trials, Meric-Bernstam says.

Mills is co-director of MD Anderson's Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy and Meric-Bernstam is medical director of the institute.

 A phase 2 clinical trial of a targeted therapy provides evidence that there might, at last, be a treatment that shrinks or stifles the growth of recurrent low-grade serous ovarian cancer.

Women who have low-grade disease tend to be younger and survive longer than those with high-grade ovarian cancer, but when their cancer persists or comes back, it almost always thwarts treatment. Between 2% and 4% of patients respond to chemotherapy.  Hormonal therapies do modestly better, with a 9% response rate.

In the clinical trial of the drug selumetinib published in the February edition of The Lancet Oncology, eight of 52 (15 percent) patients had a complete or objective partial response (tumor shrinkage) and 34 (65 percent) had no disease progression during the two-year course of the study.

"These are remarkably encouraging results for what can ultimately be a devastating disease," says David Gershenson, M.D., professor in MD Anderson's Department of Gynecologic Oncology and Reproductive medicine, the paper's senior author.

Selumetinib hasn't made Doris Elliott's recurrent low-grade ovarian cancer disappear. But it shrank all of her tumors and has arrested their development for five years running. 

For Dotsy Elliott, cancer under control for five years and counting

After her diagnosis in 1997, six rounds of chemotherapy kept  cancer at bay until 2005. Surgery and nine rounds of chemotherapy did little to slow progression. Another clinical trial helped for about 18 months.

Patients with chronic myeloid leukemia (CML) or acute lymphoblastic leukemia that carries the Philadelphia chromosome (Ph+ALL) who can't tolerate the targeted drugs that revolutionized care for these leukemias now have three new options.

The U.S. Food and Drug Administration (FDA) has approved  three new drugs in the past few months. Ponatinib (Iclusig) was approved last week, an effective drug for many patients with  treatment-resistant disease. This comes on the heels of approvals of bosutinib (Bosulif) in September and omacetaxine (Synribo) in October.

Patients with both leukemias have enjoyed strong responses to imatinib (Gleevec) and second-generation drugs nilotinib (Tasigna) and dasatinib (Sprycel).  All work by inhibiting proteins called tyrosine kinases on leukemia cells, in particular the aberrant BCR-ABL protein that causes these diseases.

However, 30-40 percent of patients' CML resists imatinib. Nilotinib and dasatinib work for about 40-50 percent of those patients.

"It's important to have as many therapies against cancer as we can, because rarely does one drug or combination succeed for all patients," said Jorge Cortes, M.D., professor in MD Anderson's Department of Leukemia.  "These new drugs cover different gaps in treatment, so they can serve our patients in different ways."

MD Anderson's two co-authors on the second study reflect the department's participation in the clinical trial. Wen-Jen Hwu was principal investigator at the MD Anderson site. In that study, researchers reported that "of 207 patients with advanced cancer who received an anti-PDL1 antibody, 6-17% of evaluable patients experienced an objective response (either complete or  partial)," Nature Medicine noted.

Despite the fact that it remains unknown why only certain tumors and patients responded to the antibodies, "these trials further validate immune modulation of T cell activity as a therapeutic approach to cancer treatment," Nature Medicine concluded.