Recently in Cancer Research Category

Cancer eludes, suppresses or subverts the body's immune system to survive and grow.  
Scientists at M. D. Anderson have found that the helper T cell Th17 awakens the immune system to attack and destroy tumors with custom-made killer T cells.  Professor of Immunology Chen Dong, Ph.D., and colleagues report their findings online today at the journal Immunity.  

Working with a mouse model of metastatic human melanoma tumors, the researchers show that the absence of Th17 led to virulent growth of melanoma in the lungs, while injecting Th17 cells prevented melanoma development and destroyed existing tumors. Th17 secretes the inflammatory protein interleukin-17 (Il-17), which launches the immune system response. 



"While there is much work to be done, these preclinical findings imply the possibility of taking a patient's Th17 cells, expanding them in the lab, and then re-infusing them as treatment," Dong said. Development of a vaccine to stimulate Th17 cells would be another possible application.

Dong is co-discoverer of Th17, one of only four known types of T helper cells that guide adaptive immune system response.  His team also established that Th17 produces interleukin-17 and further showed that overexpression of IL-17 causes both autoimmune and inflammatory diseases.  

Th17's involvement in autoimmune disease is probably why it is able to recognize and attack cancer, which is also self tissue.  "So a key to developing therapy will be to use Th17 cells that only recognize tumor antigens but do not react to normal tissue," Dong said.

Read the full News Release
AAI Honors Chen Dong for Breakthrough T Lymphocyte Research

Toad Venom May Help Treat Cancer

Huachansu, a Chinese medicine that comes from venom secreted by the skin glands of toads, may slow the growth of cancer in some patients and do so without significant side effects.

Researchers at M. D. Anderson and Fudan University Cancer Hospital in Shanghai, China, reported their Phase I clinical trial findings Aug. 21 in the online Early View feature of the journal Cancer.

Stereotactic Radiosurgery Preferred for Brain Metastases

Cancer patients who receive stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) to treat 1-3 metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone.

Findings from a Phase III randomized study led by M. D. Anderson researchers were published in the Oct. 5 online edition of The Lancet Oncology.

Cancer Newsline Podcast Series

New Breast Cancer Screening Guidelines
Therese B. Bevers, M.D., Professor in the Department of Clinical Cancer Prevention explains the newly released breast cancer screening guidelines.  Dr. Bevers discusses how the new guidelines address women at higher risk of being diagnosed with breast cancer and when and how often they should be tested by mammogram or breast MRI.

Every October, scientists and the public from around the world eagerly await the announcement of the winners of the Nobel Prize in Medicine. This year, the prize was given to three U.S. scientists for the discovery and identification of telomeres and telomerase, a process that seals off the tips of chromosomes like the cap on the end of shoelaces, and is a key to understanding both aging and cancer.

Telomeres are essentially caps that protect the ends of chromosomes. The telomerase enzyme determines the length of the caps. The longer the caps, the more frequent the chromosomes can be copied, therefore, controlling how often the cell divides.

The potential impact of this discovery is obvious. Inhibiting the enzyme activity can reduce the cell capacity to divide, a hallmark of cancer. In aging cells, the caps, or telomeres, become shorter. Thus, maintaining telomerase activity may prevent aging.

The Nobel Committee cited the scientists' work that was published approximately 30 years ago (telomeres in 1978 and telomerase in 1985). This means that two of the recipients were in their 30s and one was in her 20s when they made these discoveries.

Intriguing selection process
The secretive nomination and selection process of the committee remains intriguing, and continuously generates rumors and fascinating stories. According to Alfred Nobel's instructions in his will, the committee members should always be selected from the Karolinska Institute faculty in Stockholm.  In 1901, the committee included 19 members. Today, it includes 50. A total of 195 individuals have received the Nobel Prize in Medicine.

I visited Karolinska Institute in 1999, and had the opportunity to meet with its president, Dr. Hans Wigzell. At the time, Dr. Wigzell was the chairman of the Nobel Assembly that awards the prize in medicine. The following year I invited him to visit M. D. Anderson and to give a lecture on his scientific work in immunology. However, my hidden agenda was to get him to meet with our young medical oncology fellows, to discuss the award and to inspire them. He graciously accepted the invitation.

As planned, Dr. Wigzell met with our fellows in a small conference room over coffee and bagels. The informal meeting lasted 90 minutes, and the discussion spanned many interesting topics and anecdotes regarding the Nobel Prize. Although he couldn't reveal any secrets, he provided very important facts and insights.

The first fact was that nominations are kept very secretive and are not released to the public. You know that you got the prize when someone calls you from Stockholm early in the morning, shortly before the announcement is made public. So this is not like the Oscars. Although several investigators are nominated on a short list, the names remain secret and, therefore, there is no reward or even an acknowledgement for being nominated. Nothing to write about in your C.V.

The second fact was that no matter how important the discovery might be, the award is given only to a living scientist. No award is given after death.

The third, and most important observation that I recall from our meeting with Hans Wigzell, was that the majority of awards were given to scientists for discoveries that they made when they were young, mostly when they were in their 30s. A remarkable observation that strongly endorses the notion than many creative ideas come from young, unestablished investigators.

However, these discoveries have to be validated over time, and thus the awards are frequently given 20-30 years after their discoveries. This year's award was no exception.

Funding the young still critical
As research funds continue to decrease, a debate in the scientific community is focusing on who should get more research support: established senior investigators or new junior investigators. No one argues that established senior investigators should continue to receive research funding. However, a quick look at the history of the Nobel Prize and its laureates should convince everyone that funding young investigators is also critical for the continued progress through major discoveries that will have the greatest impact on humanity.
 

It takes some imagination to grasp the raw computational challenge researchers face trying to understand the molecular causes of cancer. John Weinstein, M.D., Ph.D., professor and chair of M. D. Anderson's Department of Bioinformatics and Computational Biology, likes to start with this imagery.

"If you unpacked the DNA in every cell of a single person and stretched it end to end, it would circle the equator 917,000 times -- the equivalent of 120 round trips to the sun. One error in replicating the genome in one unlucky place -- over a length of 120 trips to the sun and back -- can lead to cancer. Our challenges are to understand how that happens, and to know what to do about it if we can't prevent it in the first place."  

Now, consider that there are usually many more errors spread across that expanse and that they tend to interact with each other in a maze of complexity. Add current techniques to profile genetic expression and variation that capture a galaxy of data, and you have enough information to choke traditional methods of analysis.

The Cancer Genome Atlas, a federally funded project to make sense of the genetics that drive 20 different cancers, has enlisted Weinstein and colleagues at M. D. Anderson to help with this problem. A five-year, $8.3 million grant will allow the team to apply cutting-edge approaches to find the right buckets of information in an ocean of data.

They will blend agile software development, Bayesian statistics, and a flexible and efficient database infrastructure called semantic web with M. D. Anderson's expertise in clinical and translational research to compile the most meaningful data in a tumor's tangled molecular profile.

Success will mean better treatment choices, improved risk assessment, diagnosis and prognosis. "The bottom line is personalizing cancer medicine," Weinstein says.

By Susan Kelly M. D., Assistant Professor, Department of Pediatrics

What is cord blood?
When a baby is born, there are a high number of stem cells circulating in the blood that are generally discarded with the placenta. The primary responsibility of these stem cells (what we refer to as umbilical cord blood or cord blood) is to make components of blood -- red blood cells, white blood cells and platelets.

Cord blood can be collected and stored in liquid nitrogen for years and later used for transplants. There are public banks, where mothers can donate the cord blood for use by anyone who needs a transplant (at no charge). There also are private cord blood banks that allow a family to store their baby's cord blood for use by someone in the family (the family pays for its collection and storage). The cord blood units stored in public banks are searchable through a computer registry that's accessible throughout the world.

Cord blood transplants
The first transplant using umbilical cord blood was done in 1988. Since then, thousands of transplants have been performed using cord blood as the source of stem cells.

Why is this important? The first choice for a stem cell donor is usually a perfectly matched sibling (or other matched family member). We look at markers on the cells called HLA types (different than blood type) to see how closely a patient and potential donor match. Matched cells from a family member have a higher chance of taking (engrafting) and cause fewer side effects, such as graft-versus-host disease (GVHD), where the transplanted cells attack their new "host." 

However, as families are changing and getting much smaller, the chance of having a fully matched sibling is quite low. Only one in four full siblings will be a match, and half- and step-siblings are almost never a match. The other options for stem cell transplants include finding an unrelated stem cell donor or receiving stem cells from cord blood.

While the bone marrow registry is expanding, the chance of finding a match is less than 50% and much lower for minority patients or patients with mixed ethnicity. Cord blood doesn't need to be matched as closely as other stem cells because they're more naïve immunologically, causing less GVHD. Therefore, a match can be found for a much higher percentage of people.

A unique approach to understanding how cancer cells or microbes become capable of warding off drugs has earned a New Innovator Award from the National Institutes of Health for an M. D. Anderson scientist.

Gábor Balázsi, Ph.D., assistant professor in the Department of Systems Biology, will receive $1.5 million over five years under the highly competitive program. The NIH announced awards Thursday in three prestigious programs that fund bold ideas, with the potential to speedily translate research into improved human health. 



"Therapy fails when cancer cells or disease-causing microbes become resistant to drugs. We will apply new, non-conventional methods to control expression of a drug-resistance gene in cells that are then treated with chemotherapy," Balázsi says. "We expect to discover new mechanisms underlying the emergence of drug resistance, which could improve treatment of cancer and of microbial infections as well."

Balázsi and colleagues are synthetic biologists who have created gene circuits that allow them to tightly control expression of a gene, dialing it from completely off through varying levels of expression to completely on.

A newly developed circuit also will permit them to control fluctuations in gene expression. This unique degree of control will allow more detailed investigation of the effects of genes involved in drug resistance.

"These are highly competitive awards for the most innovative science. Being chosen as a recipient is a significant accomplishment," says M. D. Anderson Provost and Executive Vice President Raymond DuBois, M.D., Ph.D.  "His research concept is exciting and holds promise for improving our ability to adjust very specific cellular levels of a variety of genes and then test drug resistance, among other things."


Read the News Release
M. D. Anderson Scientist Wins NIH New Innovator Award

By Tomise Martin, Staff Writer

Inspired by her passion to help others and her courageous fight with a rare disease, family and friends of Marnie Rose, M.D., have donated more than $1 million to brain cancer research at M. D. Anderson.

"The Dr. Marnie Rose Foundation is named after my daughter who died from a malignant brain tumor at age 28," said Lanie Rose, mother of Marnie. "She was beautiful, bright and as a pediatric medical resident, she devoted her life to caring for children. Through the foundation, we honor her legacy by helping both children and brain cancer patients in need."

All funds raised by the Dr. Marnie Rose Foundation for M. D. Anderson go directly to research of treatments. With guidance from Raymond Sawaya, M.D.and Alfred Yung, M.D., professor and chair of the Department of Neuro-Oncology the foundation has funded five research projects over the last seven years. Two of those therapies funded, PEP-3-KLH, a therapy that trains the immune system to attack brain tumor cells, and Delta-24-RGD, a modified adenovirus that targets the pathway of a specific protein, have shown promising results in the lab and are now in clinical trials.



"Since 2003, we've been able to sponsor brain cancer patients and fund clinical trials for immunotherapy and other research," Lanie said. "During M. D. Anderson's annual patient conference for brain tumor patients, a young man thanked our foundation for our help in his care. Because of the research our foundation supports, he joined a clinical trial that provided innovative treatment."

Resources

Run for the Rose 5K Fun Run

By Wendy Gottsegen, Director, External Communications

We also don't recommend that you don't drink the water, either. Confused? Well there seems to be buzz on the Internet about a type of water that a Dallas-based company is marketing and this water's relationship to M. D. Anderson.   

So we thought we'd un-muddy the water for our patients, employees and supporters. M. D. Anderson doesn't recommend the water. 

What we did do was test the water (this time the pun is not intended) for the company, who compensated us to do so. The tests were very specific, not comprehensive and the results were turned over to the company without interpretation by M. D. Anderson experts.

Recent research at M. D. Anderson shows that obesity is a risk factor for pancreatic cancer, and being overweight may play a role in the outcomes of people who develop the disease.

Donghui Li, Ph.D., professor in M. D. Anderson's Department of Gastrointestinal Medical Oncology and the study's senior author, answers questions about this landmark investigation.

What inspired you to do this study?
We know obesity is a risk factor for pancreatic cancer, but few studies have looked at body mass index (BMI) throughout a patient's lifetime rather than just when they are adults or the year they are diagnosed. We wanted to show the relationship between BMI and the risk of developing pancreatic cancer across a patient's life span and determine if being overweight in a specific time period raised that risk.

Also, we were curious about the links among BMI, cancer occurrence and overall survival.
Why is this study important?

Pancreatic cancer is one of the most dangerous types of cancer. It's the fourth leading cause of cancer death in men and women in this country. Median survival is less than 10 months, and the five-year survival rate is less than 5%.

Obesity and smoking are known risk factors for the disease, and while smoking is on the decline, obesity is increasing.

This study helps us understand the cause-and-effect relationship between obesity and pancreatic cancer, and we hope it will help identify high-risk people and specific ways to prevent them from getting the disease.

What were the research methods?
First, we enrolled 1,595 people:
•    841 pancreatic cancer patients treated at M. D. Anderson from 2004 to 2008
•    754 cancer-free people

We interviewed each person about his or her:
•    Smoking history
•    Family cancer history
•    Alcohol use
•    Medical history

Participants were asked to recall their height and body weights at 14 and 19 years old; in their 20s, 30s, 40s, 50s, 60s and 70s; and the year prior to their pancreatic cancer diagnoses or enrollment in the study.

We then calculated each person's BMI during each decade and compared the healthy patients with the pancreatic cancer patients.

Among the cancer patients, we also looked at the average age of diagnosis and the overall survival time, then compared those to their BMIs.



What were the results?
As we suspected, the research confirmed an association between obesity and pancreatic cancer.

People who were obese when they were young had a higher risk of developing pancreatic cancer than those who became overweight later in life.
For example, people who became overweight:
•    Between 14 and 19 years old had 100% increased risk
•    In their 20s had 65% increased risk
•    In their 30 had 27% increased risk

The risk of developing the disease diminished for those who gained excess weight in their 40s and later in life.

Also, we found an association between excess weight and earlier onset of pancreatic cancer. Median age at diagnosis was 64 for those at normal weight, compared to 61 and 59 for overweight and obese patients respectively.

Obesity later in life, especially within a year before a patient's cancer diagnosis, reduced overall survival time.

Did these results surprise you?
It was surprising that overweight and obese pancreatic cancer patients were diagnosed at a younger age. This underscores the impact of obesity on loss of life, especially in productive years.

What do these results mean for pancreatic cancer?
Obesity is a risk factor that can be controlled. This study shows that we should try hard to help people control their weight at an early age to reduce the risk of pancreatic cancer.

What's next?
We need to further investigate the links among obesity, pancreatic cancer and poor outcome, looking at insulin resistance as a possible mechanism.

We also will research factors, such as heredity, diet and others, that might affect the relationship between excess body weight and the disease. One day, we hope to develop ways to prevent this dangerous cancer and detect it earlier.

Related article:
After Pancreatic Cancer, 'Southern Style' Gets A Healthy Makeover

M. D. Anderson resources:

Pancreatic Cancer (M. D. Anderson)

M. D. Anderson Study Finds Even Stronger Relationship Between High Body Mass Index,
Pancreatic Cancer (M. D. Anderson News Release)

Four New Targets Found for Breast Cancer
Protein Receptors, Enzyme Often Over-Produced

 Three protein receptors and an enzyme that often are over-produced in several types of cancer also play roles in breast cancer.

A team of researchers, led by scientists at M. D. Anderson, reported its findings on lysophosphatidic acid (LPA) receptors (LPA1, LPA2, and LPA3) and the LPA-producing enzyme, autotaxin, in the June edition of Cancer Cell.

"Lysophosphatidic acid is the single most potent cellular survival factor," says
Gordon Mills, M.D., Ph.D., professor and chair of M. D. Anderson's Department of Systems Biology and senior author on the paper.


Variation in Gene May Increase Risk of Bladder Cancer
Prostate Stem Cell Antigen (PSCA) Is a Factor

Researchers have pinpointed a specific gene variation that causes increased risk of urinary bladder cancer.

In the future, scientists hope the results of this large, multicenter international study may help determine who is at high risk for this deadly cancer, which may lead to improved screening and targeted chemopreventive interventions.

"With this research, we found a novel specific gene and a functional variation that are independent of the previous suspects," says Xifeng Wu, M.D., Ph.D., professor in M. D. Anderson's Department of Epidemiology, the lead and corresponding author.


Five Gene Variations Raise Risk for Brain Tumors
Study Is First to Discover Glioma Risk Factors

Variations in five genes may raise a person's risk of developing glioma, the most prevalent type of brain tumor.

This study, the first to suggest risk factors for any type for glioma, was the largest to date of a rare cancer. The international research team, led by scientists at M. D. Anderson and the Institute of Cancer Research in the United Kingdom, reported its findings online in Nature Genetics.

"This is a groundbreaking study because it's the first time we've had a large enough sample to understand the genetic risk factors related to glioma, which opens the door to understanding a possible cause of these brain tumors," says co-senior author Melissa Bondy, Ph.D., professor in M. D. Anderson's Department of Epidemiology.
Video - Genetic Variants Linked to Brain Tumor Risk


Cancer Newsline Audio Podcast Series

Anal Cancer
Cathy Eng, M. D., associate professor in the department of gastrointestinal medical oncology explains risk factors and treatment options for anal cancer.

Treatment Options for Lymphedema Patients
David Chang, M.D., explains what lymphedema is and discusses treatment options including lymphaticovenular bypass surgery.

How Common Is Use of Off-Label Drugs in Breast Cancer?
Many Patients Receive Legal But Non-Approved Drugs

 More than one-third of breast cancer patients receive chemotherapy drugs that, while approved by the U.S. Food and Drug Administration (FDA), have not been vetted specifically to treat the disease.

The use of drugs for conditions other than those for which they were approved is legal, and, according to a study by M. D. Anderson researchers, prevalent in breast cancer treatment. The study was presented at the American Society of Clinical Oncology's (ASCO) annual meeting in May.

Vaccine Gives Hope Against Advanced Melanoma
First-of-Its-Kind Study Shows Benefit

Patients with advanced melanoma, one of the most dangerous cancers, showed improved response to treatment and length of progression-free survival when a vaccine was added to their treatment with the immunotherapy drug interleukin-2 (IL-2).

Results from the Phase III clinical trial - the first of its kind in melanoma and one of the first in any type of cancer - were presented by M. D. Anderson researchers at the American Society of Clinical Oncology (ASCO) annual meeting in May.

Two-drug Combo Shows Benefit in Lung Cancer
Targeted Agent, Chemotherapy Slow Cancer Growth

When combined with the standard chemotherapy drug Taxotere® (docetaxel), the oral targeted therapy Zactima® (vandetanib) improves progression-free survival for patients with advanced non-small cell lung cancer.

Researchers from M. D. Anderson presented the findings of the first-of-its-kind, international Phase III trial at the American Society of Clinical Oncology's (ASCO) annual meeting in May.

Cancer Newsline Audio Podcast Series

Hodgkin's Lymphoma Treatment Anas Younes, M.D., Professor of the Department of Lymphoma/Myeloma discusses frontline, pre-transplant, and post-transplant treatment options for Hodgkin's lymphoma.

Ways You Can Help Without Giving Money: Donate Blood
Andrea Johnson, Community Representative for the University of Texas M. D. Anderson Blood Bank, discusses the challenges blood banks face when getting blood and platelets for their patients and explains how you can help.

The mission of M. D. Anderson's Odyssey Program is to support the best among the newest generation of cancer researchers here and encourage them to explore novel areas of clinical, translational, basic or population-based cancer research. To fulfill this mission, the Odyssey Program supports them and their research during their post-doctoral training, a critical career phase during which scientists first develop independence and a funding track record.

Odyssey Fellowships are given annually, with a start date of Sept. 1, following an open call for applicants and a rigorous peer-review process. This round we had 41 applications from 26 departments and were able to support three new fellows, about 7%, making the Odyssey Program's competition one of the toughest. You can compare this to the National Institutes of Health payline, which even in the toughest times has stayed above 10%.

The three awardees who will join the Odyssey Program in 2009 are:

• Dr. Calley Hirsch from Dr. Sharon Dent's lab (Department of Genetics): "The Role of Gcn5 in Mouse Embryonic Stem Cells"

• Dr. Marites Melancon from Dr. Jason Stafford's lab (Department of Imaging Physics): "Targeted Nanoshell-Based Agents for MRI-Guided Thermal Ablation of Head and Neck Cancer"

• Dr. Sofie Claerhout from Dr. Gordon Mills' lab (Department of Systems Biology): "Tumor Dormancy and Autophagy -- Implications for Breast Cancer"

I want to thank the Odyssey Program Advisory Committee for their hard work in scoring these applications.

The Odyssey Program is supported by  endowments from the Theodore N. Law Award For Scientific Achievement, Houston Endowment, Inc. Award for Scientific Achievement, H-E-B Award for Scientific Achievement, Kimberly-Clark Foundation Award for Scientific Achievement, Cockrell Foundation Award for Scientific Achievement, The Kimberly Clark Fund for New and Innovative Research. Recently the program has received generous support from the CFP Foundation and the Arnold Family Foundation.