Golfers at last year's Vora brothers "Heads Up For Head and Neck Cancer" fundraiser trying to act natural. Not hamming it up at all.

Head and neck cancer patients with a history of smoking have the worst prognosis. A new clinical trial conducted only at the University of Colorado Cancer Center will use a novel combination of two drugs with radiation to help increase the odds for this population.

Funding for this unique clinical trial comes in part from the 5th annual “Heads Up For Head and Neck Cancer” golf tournament, sponsored by brothers Kuntal and Rahool Vora in loving memory of their father, Naren A. Vora. The tournament will take place Saturday, June 16th at the Raccoon Creek Golf Course in Littleton, CO. Shotgun start is at 7:30am. Registration is linked above.

“It costs at least $5,000 dollars to cover a single patient on a clinical trial and so these funds will be very important to support what we believe is one of the most innovative clinical trials for head and neck cancer in the United States,” says David Raben, MD, director of head/neck radiation oncology research at the CU Cancer Center.

It doesn’t hurt that if you hit a hole-in-one on the par-3 17th hole, you can drive home a 2013 Lexus.

If this fun event doesn’t fit your schedule, consider emailing the Vora brothers at NAVMGT@gmail.com to sponsor the event or donate money and/or raffle items.

Image: Flickr/RobEllis cc license

THREE KEY POINTS:

• Presence of the proteins RalA and RalB predict aggressive human cancers
  
• RAL proteins change gene expression — signatures of these changed genes predict cancer stage and shorter survival
  
• RAL proteins are a likely target for cancer therapies
  

We have known for years that when the proteins RalA and RalB are present, cells in dishes copy toward aggressive forms of cancer. However, until this week, no study had explored the effects of RAL proteins in human cancers – an essential step on the path to developing drugs to target these proteins. From metastasis in bladder cancer, to seminal vessel involvement in prostate cancer, to shortened survival in squamous cell carcinoma, a study published this week in the journal Cancer Research shows that RalA and RalB are associated with aggressive cancer characteristics in human tumors.

“But here’s the interesting part,” says Dan Theodorescu, director of the University of Colorado Cancer Center and the paper’s senior author – “it wasn’t the presence of these proteins per se that predicted aggressive cancer characteristics, it was the signature of other genes changed by RAL activity in the cells that predicted poor outcomes.”

RalA and RalB activity leads to a cascade of genetic (and gene expression) changes. Theodorescu and colleagues discovered the signature of these changes, and this pattern of turning up and turning down genes is what predicts aggressive cancers.

“It might not be presence of these RAL proteins themselves that drives cancer as much as their ability to drive genetic changes that in turn drive cancer,” Theodorescu says.

In the three types of human tumors explored – bladder, prostate, and the skin cancer known as squamous cell carcinoma – panels of genes affected by RalA and RalB in turn predicted stage and survival.

“The RAL family of GTPases are cousins of the now well-known RAS family of oncogenes,” Theodorescu explains. “These RAS family GTPases, are found in leukemias, lung cancer, colon cancer and others, and have been a focus of efforts to develop targeted cancer therapies. We imagine the related RAL family may provide a similar target.”

Remove RalA and RalB from cancer cells and perhaps doctors can stop the genetic changes that cause aggressive cancer.

—

Support provided by National Institutes of Health, National Cancer Institute grant CA075115

Image: Flickr/HealthyRX cc license

THREE KEY POINTS:

• Taken at more than 10x RDA, beta-carotene, selenium and folic acid are proven to increase cancer risk
  
• Full biological effects of dietary supplements are unknown
  
• Supplements lack the FDA regulation afforded to “drugs”
  

Beta-carotene, selenium and folic acid – taken up to three times their recommended daily allowance, these supplements are probably harmless. But taken at much higher levels as some supplement manufacturers suggest, these three supplements have now been proven to increase the risk of developing a host of cancers.

“It’s not that these nutrients are toxic – they’re essential and we need them, but we need them in a certain balance,” says Tim Byers, MD, MPH, professor of epidemiology at the Colorado School of Public Health and associate director for prevention and control at the University of Colorado Cancer Center.

Byers is senior author of a commentary recently published in the Journal of the National Cancer Institute that discusses the clinical and policy implications of the increased cancer risk from high dose dietary supplements.

“We have a window into less than half of the biology of what these nutrients are doing,” Byers says. “We say generalized things about them, calling them an antioxidant or an essential mineral, but true biology turns out to be more complex than that. The effects of these supplements are certainly not limited to the label we give them. And, as we’ve seen, sometimes the unintended effects include increased cancer risk.”

Currently the FDA regulates dietary supplements as food, but, as Byers and colleagues suggest, supplements, especially at high doses, are more accurately described as inhabiting a mid-ground between food and drugs. Like drugs, supplement ingredients are biologically active – sometimes for better and sometimes for worse.

“We need to do a better job as a society in ensuring that the messages people get about value versus risk is accurate for nutritional supplements,” Byers says. “My conclusion is that taking high doses of any particular nutrient is more likely to be a bad thing than a good thing.”

—

This work was supported by the National Institutes of Health, National Cancer Institute CA140285

E. David Crawford, MD, CU Cancer Center investigator, will accept the Robert J. Krane Prize for the Best Clinical Paper of 2011 in the British Journal of Urology International

A high level of prostate-specific antigen (PSA) predicts prostate cancer – about 30 percent of men with PSA over 4.0ng/ml have the disease. And until recently, below 4.0ng/ml was considered fairly safe. A University of Colorado Cancer Center paper shows that even at PSA levels between 1.5-4.0ng/ml, a man’s chance of having prostate cancer increases 15-fold.

The finding was chosen the year’s top publication in the British Journal of Urology International.

“We call this the ‘early warning PSA zone’,” says E. David Crawford, MD, investigator at the CU Cancer Center and the study’s lead author.

Specifically, Crawford’s study examined data from at 21,502 men over age 40 who were found to have between 0 and 4.0ng/ml PSA, and who were then tested again at least four years later. Which of these men testing in the “normal” PSA range were later found to have prostate cancer? Well, 7.85 percent of men with PSA levels between 1.5-4.0ng/ml compared to only 0.51 percent of men below this concentration were later found to have the disease. The risk in the “normal” population was even a bit higher for African American males, who were found to have a 19-fold increase in prostate cancer rates as PSA passed 1.5ng/ml.

“This is a robust finding,” Crawford says, “and it has the potential to make doctors and other caregivers rethink how we interpret PSA levels.”

Crawford will accept the Robert J. Krane Prize for the Best Clinical Paper of 2011 at the annual meeting of the American Urological Association, May 20, 2012 in Atlanta, Ga.

Petri dish, courtesy of Flickr/GavinRice cc license

THREE KEY POINTS:

• Human tumors, sampled and grown on mice are more accurate cancer models than cell lines grown on plastic
  
• Human-derived “xenografts” are more genetically are structurally similar to patient tumors
  
• Patient-derived tumor models can help predict who will respond to new, targeted cancer treatments and how to overcome a tumor’s treatment resistance
  

Sampling human tumors and incubating them on mouse models is more accurate than standard cell lines grown on plastic, writes a paper from the University of Colorado Cancer Center, recently published in the journal Nature Reviews: Clinical Oncology. These patient-derived “xenograft” models are more likely to respond as would real tumors when treated with experimental cancer therapies. The more accurate response of these human-derived tumors can help speed the pace of cancer drug development from lab to clinic.

“There are two major problems with cell lines grown on plastic,” says John Tentler, PhD, investigator at the University of Colorado Cancer Center, associate professor at the University of Colorado School of Medicine and the paper’s lead author. “First, if cells are grown on plastic, we can hit them with defined, uniform concentrations of test drugs – this isn’t the case in human tumors, in which a drug’s ability to penetrate the tissue might be as important as its effectiveness once it reaches its target. And second, when you grow cells on plastic, they change their genetic characteristics.”

“If you think about it, it makes sense,” says S. Gail Eckhardt, MD, CU Cancer Center investigator and the paper’s senior author. “You take cells that have had a three-dimensional life and shock them on plastic – they have to evolve to live on that, and they’ll grow new features and lose some of their original genetic characteristics.”

Eckhardt also points out that most commercially available cells lines are decades old, allowing hundreds of generations after which they may evolve genetic characteristics that differ from the original, parent tumor.

And so the University of Colorado Cancer Center is leading the way toward another method of maintaining tumor tissues.

“We’re one of the few academic centers in the country to have a large and varied platform of patient-derived tumors,” says Antonio Jimeno, MD, PhD, director of the Head and Neck Cancer Medical Oncology Program at the CU Cancer Center. Tumor samples are taken from consenting surgery patients and then grown in mice. The CU Cancer Center maintains about 30 cases of human colon cancer, 30 cases of head and neck cancer, 15 cases of melanoma, and other lines including breast, pancreatic and bladder cancers.

“This is a better way of doing drug development,” Jimeno says. In addition to accuracy, Jimeno points out that patient-derived tumors can quickly add tumor types not represented in currently available cell lines. “For instance, there are no cell lines of human papillomavirus-related head and neck cancer, and we have several strains growing from our patients,” Jimeno says.

And Eckhardt explains that these models can help prove the effectiveness of new cancer drugs. Today’s targeted therapies don’t work on just any cancer – they’re pointed at the very individual genetic features of very individual cancers. If you test a targeted drug with a general population, it can look ineffective – maybe only a small percentage of patients benefit. But if you use these patient-derived mouse models to see which tumors respond (and which don’t), you can predict which patients will be among the small percentage of responders. You can also design a clinical trial to include only these patients who are likely to benefit. “It’s as if you’ve enrolled 30 or 40 ‘xenopatients’,” Eckhardt says.

These models can also be used on what is effectively the back end of a clinical trial, to explore how doctors might overcome a tumor’s resistance to a first-line therapy. “You treat mice with a first drug X for period of time, until these human tumors grown on mice become resistant, then you analyze the pathways of this resistance, and finally test what might overcome this resistance,” says Colin Weekes, MD, PhD, CU Cancer Center investigator and paper co-author. Weekes also points out that a tumor isn’t a homogenous lump. It’s made up of a variety of cells, and so experimenting on a homogenous mat grown on plastic is likely to give different results than experimenting on a more complex, human-derived tumor.

In these ways, human-derived tumor models help cancer drugs vault over cell lines and into clinical trials and ultimately patients.

More details are available on the website at
http://www.surgonc.org/grants–trials/research-grants/clinical-investigator-awards/clinical-investigator-award-in-breast-cancer-research.aspx

Founded in 1940, the Society of Surgical Oncology (SSO) promotes the highest quality of surgical oncology care by advancing the training and education of its members and fostering oncology research to improve the multidisciplinary care of cancer patients.

Clinical Investigator Award in Breast Cancer Research
The purpose of this award is to promote patient-oriented breast cancer research conducted by surgical oncologists in clinical and translational science.  The award will be funded for two years at $100,000 ($50,000 per year) beginning October 1, 2012.

James DeGregori is no stranger to cycling or to the Leukemia & Lymphoma Society.

At the age of 10, DeGregori became a commuter cyclist, biking back and forth to school. Today, more than 30 years later, he still commutes 20 miles a day to and from the University of Colorado Cancer Center, where he co-directs the center’s Molecular Oncology Program.

James DeGregori (back row, third from right) and other Team In Training cyclists at a Saturday morning ride. Photo courtesy of James DeGregori.

“I greatly enjoy cycling to work,” says DeGregori, PhD, professor of biochemistry and molecular genetics at the University of Colorado School of Medicine. “It’s a great way to stay healthy and it guarantees exercise every day.”

With years of cycling under his belt, including a couple two-day, 150-mile rides for multiple sclerosis, DeGregori decided it was time to support an organization that’s funded his research for 12 years—The Leukemia & Lymphoma Society (LLS). To date, LLS has given more than $2 million to DeGregori ‘s lab.

On June 3, DeGregori and his brother, Roger, will participate in the America’s Most Beautiful Bike Ride, a 100-mile ride in Lake Tahoe, Cali., with the Leukemia & Lymphoma Society’s Team In Training cycling program. In years past, DeGregori has participated in the LLS’s Light The Night Walk, but this year he says he needed to “macho it up a notch.”

“Team In Training isn’t just an opportunity to get out and ride bikes,” says DeGregori, who hopes to raise $10,000 for LLS. “It’s about raising awareness for LLS and helping to find cures for blood cancers.”

Multiple grants, multiple escape routes

Since 2000, DeGregori has been working to develop targeted therapies for treating acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Compared to standard cancer treatments like chemotherapy and radiation, which harm both cancer cells and healthy cells, targeted therapies can be better at selectively killing cancer cells.

James DeGregori is raising funds and awareness for the Leukemia & Lymphoma Society through Team In Training. Photo courtesy of James DeGregori.

While targeted therapies sound great, cancer cells are devious and often have fallback pathways to escape these treatments. Thanks to funding from LLS, DeGregori and other CU Cancer Center researchers are closing these cancer escape routes, one by one.

In collaboration with Chris Porter, MD, CU Cancer Center investigator and pediatric oncologist at Children’s Hospital Colorado, DeGregori is developing new combinatorial therapies for CML that target calcineurin signaling and Bcr-Abl, an abnormal protein found in CML patients. Through a clinical trial run by Porter, the two researchers are combining the drug dasatinib with cyclosporine to see whether the combination treatment is better than only treating with dasatinib.

“We still need targeted therapies with fewer side effects,” DeGregori says. “What we have right now isn’t as effective as we want it to be, so we need a one-two punch or maybe a third punch to knock out multiple dependencies at once. While we’ve made progress, we’re certainly not ready to rest on our laurels.”

Additionally, DeGregori is working with Douglas Graham, MD, PhD, CU Cancer Center investigator and pediatric oncologist at Children’s, to target similar pathways in AML. They hope their initial work will lead to a clinical trial by the end of 2014 when their three-year LLS grant is up.

“The Leukemia & Lymphoma Society is truly funding research from bench to bedside,” DeGregori says.

Beyond research, it’s personal

When the DeGregori brothers participate in the Tahoe bike ride, they won’t just be cycling for the Leukemia & Lymphoma Society. They’ll be riding for the friends and family members they’ve lost to leukemia and lymphoma: an aunt, a cousin, a niece in Argentina, a friend, and a host-father in Uruguay, where DeGregori was a high school exchange student.

DeGregori says, had his host father been diagnosed 10 years later, he’d likely be a survivor. The drug Gleevec, which dramatically improved CML survival, was approved by the Federal Drug Administration in 2001. The research for this drug was heavily funded by LLS.

“I really believe in the LLS,” DeGregori says. “I’ve had multiple family members that I’ve lost due to leukemia and lymphoma so this ride is also personal. I know the toll blood cancers can take on patients and their families.”

Every Saturday, DeGregori meets other Team In Training participants for a training ride. At the beginning of each ride there’s a “mission moment” or time for someone to share their reason for participating in Team In Training. There’s never silence, says DeGregori.

“Pretty much everyone on my team knows someone who’s had some form of blood cancer so they all have stories to tell.”

For DeGregori, his story is three-fold: leukemia researcher, LLS grantee and family member.

***

Since 1988, Team In Training has raised more than $1.2 billion to fund cancer research. To donate to DeGregori’s ride for the LLS, please visit: http://pages.teamintraining.org/rm/ambbr12/jdegregori.

· Blood cancers

· Colorectal cancer

· Genetic cancer research

· Kidney cancer

· Listeria vaccine for cancer

· Melanoma and other skin cancers

· Mesothelioma

· Pancreatic cancer

· Pediatric brain tumors

The program is administered by the USAMRMC through the Office of the Congressionally Directed Medical Research Programs (CDMRP).

FY12 PRCRP Program Announcements and General Application Instructions for the following award mechanisms are posted on the Grants.gov website. http://cdmrp.army.mil/funding/prcrp.shtml

Visionary Postdoctoral Fellowship Award – Pre-application due date June 19, 2012
Eligibility – Principal Investigator: M.D./Ph.D. graduate with a total of less than 4 years of postdoctoral research experience

Mentor(s): Independent investigator at the level of Assistant Professor or equivalent at the time of the award

Key Mechanism
Research must be in one or more of the FY12 PRCRP Topic Areas

Supports training of postdoctoral fellow in the laboratory of an early-career investigator (mentor) with expertise in one or more of the FY12 PRCRP Topic Areas

Supports training of postdoctoral fellow to include a budget option for research supplies

Applications must not address breast, prostate, lung (excluding mesothelioma), or ovarian cancer research

Preliminary data not required

Clinical trials will not be supported

Funding
Maximum funding for the entire period of performance is $240,000 for direct costs (plus indirect costs)

Maximum period of performance is 3 years

Career Development Award – Pre-application due date June 19, 2012
Eligibility – Principal Investigator: Independent investigator at the level of Assistant Professor or equivalent at the time of the award

Key Mechanism Elements
Research with emphasis in discovery must be in one or more of the FY12 PRCRP Topic Areas

Supports investigator in the early stages of their career

Applications must not address breast, prostate, lung (excluding mesothelioma), or ovarian cancer research

Preliminary data not required

Clinical trials will not be supported

Funding
Maximum funding for the entire period of performance is $240,000 for direct costs (plus indirect costs)

Maximum period of performance is 2 years

All proposals must conform to the final Program Announcement and General Application Instructions (including deadlines) that are available for electronic downloading from the Grants.gov website. The application package containing the required forms for each award mechanism can also be found on Grants.gov.

A pre-application is required and must be submitted through the CDMRP eReceipt website http://cdmrp.org  prior to proposal submission dues date of June 19, 2012. Applications must be submitted through the federal government’s single-entry portal, Grants.gov http://www.grants.gov.

Point of Contact:
CDMRP Help Desk

301-682-5507

help@cdmrp.org

Cancer survivors are wanted for a post-treatment clinical trial of a program to help them manage common health and mental health issues.

University of Colorado Cancer Center is looking for cancer survivors in Colorado Springs to take part in a clinical trial of a program aimed at helping them manage their condition more effectively. The program, called “Cancer: Thriving and Surviving,” is adapted from a method proven effective by helping people manage other chronic conditions like diabetes and arthritis. Nearly 150 people have participated, half of the study recruitment goal.

With more than 12 million cancer survivors nationwide, researchers would like to know if programs that have proven effective in helping people manage fatigue, frustration, pain and stress might also work for managing similar issues associated with cancer.

“A cancer survivor’s journey does not end after treatment. And therapies and surgeries can have long lasting physical and emotional impact. If proven effective, ‘Cancer: Thriving and Surviving’ can help improve the quality of life for cancer survivors worldwide.  The response has been outstanding and participants to date have been extremely committed and found value in the program”, said Betsy Risendal, PhD, assistant research professor at the Colorado School of Public Heath and the trial’s principal investigator.

Cancer survivors can suffer numerous long-term complications including depression, difficulty concentrating and neuropathy.

The program, the first of its kind in the country, has been adapted especially for cancer survivors. Covered topics include communication with health care providers and family members regarding a cancer diagnosis, how to improve and maintain health and problem solving. The instructors, many of whom are themselves cancer survivors, are specially trained to lead the sessions.  The program helps link people with resources in their community after their cancer diagnosis and medical treatments.

Self-management is a focal area of health care reform and many organizations such as Centers for Disease Control and the American Cancer Society have identified self-management as a priority area.

To learn more, please call the Consortium for Older Adult Wellness at 303-956-8908 or toll free at 888-900-2629.  You can also call Memorial Health System Cancer Center at 719-365-5267.

The class will meet weekly for about two hours and for seven weeks. Cancer survivors and their caregivers are welcome to participate. The classes are available in Colorado Springs and Denver metro area and they may be offered in northern Colorado and rural communities later this year.

Ana B. Oton, MD, CU Cancer Center investigator

THREE KEY POINTS:

• On average, Hispanic lung cancer patients survive longer than other ethnic groups
  
• Researchers suspect genetic reasons for this increased survival
  
• A new study from NCI and partners including the University of Colorado Cancer Center will search for the genetic “biomarkers” of this increased survival
  

The Los Angeles Time reports that despite fewer resources and less access to care, Latino lung cancer patients in the U.S. survive longer than their non-Latino white and black counterparts. A study now underway at University of Colorado Cancer Center consortium partner, Denver Health Medical Center, and elsewhere hopes to discover why.

“Here at Denver Health and the University of Colorado, we’ll be sequencing the genomes of Hispanic lung cancer patients to see if we can discover biomarkers that make these patients especially resistant to the disease,” says Ana B. Oton, MD, CU Cancer Center investigator and assistant professor of medical oncology at the University of Colorado School of Medicine.

A $25,000 grant from the new small grants program at Denver Health, Colorado’s primary “safety net” hospital, will allow Oton to complete genetic analysis of her Hispanic lung cancer patients, even though the study is overseen by the National Cancer Institute (NCI) and includes multiple centers in the United States and Mexico.

“It’s not a lot of money, but it will allow us to contribute our small part to this NCI study,” Oton says.

Once Oton and other site coordinators have gathered data from approximately 500 Hispanic lung cancer patients, investigators should be able to discover what in these genomes correlates with increased survival. Additional analysis including genetic verification of patients’ ethnicity will be done by NCI.

“I think there’s a very strong chance of discovering exciting biomarkers, something new, that makes the Hispanic population experience better survival,” Oton says.

This low cost, high reward research has the potential to point to new, genetically targeted treatments for Hispanic and non-Hispanic populations alike.