New Test Helps Assess Colorectal Cancer Risk

A new assessment tool can help individuals calculate their risk for colorectal cancer, also known as cancer of the colon or rectum. The test designed by National Cancer Institute (NCI), the University of Utah, and the Kaiser Permanente Medical Care Program of Northern California is now available online.

With more than 108,000 new cases of colon cancer and more than 40,000 new cases of rectal cancer, colorectal cancer is the fourth most common cancer in men and women in the United States and the second leading cause of cancer-related deaths. The symptoms can remain undetected for many years and in most cases will develop quite slowly. However, as a result of better detection and treatment, the death rate from colorectal cancer has been dropping. Caught early, colorectal cancer is often curable.

The new assessment tool is designed for people 50 years of age and older and based on data collected from two large US population-based case control studies of colon and rectal cancer, data from 13 NCI Surveillance, Epidemiology and End Result Registries (SEER data), and the US national mortality rates.

How it works
The Colorectal Cancer Risk Assessment Tool uses the respondent’s answers about risk and preventive factors to calculate that person’s absolute risk for developing colorectal cancer for a specific time period. The online test is interactive, simple and straightforward and takes only 5-8 minutes to complete. After answering the questions, the tool will calculate an individual’s risk for colorectal cancer.

To validate the accuracy, the model was tested in a large population. The results show that the tool is accurate in predicting absolute risk. Because the majority of participants in the case-control studies were non-Hispanic white males and females, relative risks for other racial or ethnic groups could not be estimated. Researchers are in the process of updating the tool by using SEER rates for minority populations to allow the tool to produce more accurate results for men and women in these populations. When available, the expanded functionality will include additional ages and racial/ethnic groups.

The risk calculator will be updated periodically as new data or research become available. In addition, the tool may prove useful to researchers who are designing research intervention studies.

Man and Women
To help assess the risk for, the tool is gender specific. For men, the model included a cancer-negative sigmoidoscopy/colonoscopy in the last 10 years, polyp history in the last 10 years, a history of colorectal cancer in a first-degree relatives, use of aspirin and nonsteroidal anti-inflammatory drug (NSAID), cigarette smoking, body mass index (BMI), current leisure-time vigorous activity, and vegetable consumption.

For women, the model included sigmoidoscopy/colonoscopy, polyp history, a history of colorectal cancer in a first-degree relatives, aspirin and NSAID use, BMI, leisure-time vigorous activity, vegetable consumption, hormone-replacement therapy (HRT), and estrogen exposure on the basis of menopausal status.

Better Understanding
The tool is designed to assist health care providers in counseling their patients. A better understanding of the risk will help patients and their doctor make more informed choices about how to screen and which screening tests they should take to detect signs of cancer before symptoms appear.

Although the questionnaire is suitable for 'self-administrations', researchers stress that it’s important that patients talk with their primary health care provider about the results. Commenting of the test they claim ‘The test is designed to be used by health professionals and their patients. If patients are using the tool at home, we encourage them to discuss the results, and their individual risk of colorectal cancer with their healthcare provider.’

For more information:

• The new tool is now available online.
• SEER: Surveillance, Epidemiology, and End Results Colon & Rectum (statistics).

Also, read PubMed abstracts:

• Freedman AN, Slattery ML, Ballard-Barbash R, et al. A colorectal cancer risk prediction tool for white men and women without known susceptibility. J Clin Oncol. 2008 Dec 29. [Epub ahead of print].
• Park Y, Freedman AN, Gail MH, et al. Validation of a colorectal cancer risk prediction model among whites 50 years old and over. J Clin Oncol. 2008 Dec 29. [Epub ahead of print].

Patient information:

• National Cancer Institute: Understanding cancer risks
• NIH senior health: colorectal cancer
• MedlinePlus: colorectal cancer

Organizations to contact:

• Colon Cancer Alliance - USA
• Colon Cancer Concern (The Bowel Cancer Charity) - United Kingdom
• Europa Colon - Europe

Upcoming Phoenix conference highlights 'molecular oncology' for oncologists and their patients

Physician-scientists from the Arizona based Translational Genomics Research Institute (TGen), a non-profit organization dedicated to conducting groundbreaking medical research in with life changing results, and Scottsdale Healthcare, a primary clinical research site for TGen in the Virginia G. Piper Cancer Center in Scottsdale, AZ, will present their latest findings and techniques at a national conference designed to provide cancer doctors with new treatments for their patients.

'Molecular Oncology: The Sixth Vital Sign, What Every Oncologist Should Know' is intended to help oncologists provide better diagnosis, early detection as well as drugs and other treatments that in some cases can slow the growth or even shrink tumors.

'Given the explosion of new information on the genetic and cellular features of malignancy, the modern oncologist must master the significance and application of cancer-related sciences,' said Dr. Ramesh K. Ramanathan, Medical Director of TGen Clinical Research Services at Scottsdale Healthcare, a partnership between TGen and Scottsdale Healthcare Corp.

Personalized Medicine
Beyond the five vital signs of pulse, respiration, temperature, blood pressure and pain, is a new sixth 'vital sign' – molecular therapeutics. This new 'vital sign' offers oncologists the opportunity to identify the causes of disease at the molecular level in order to provide the right drugs in the right amounts at the right times for the specific needs of individual patients. This new approach is becoming better known in health circles as personalized medicine or theragnostics.

However, the the concept that information about a patient's genotype or gene expression profile can be used to tailor medical care to an individual's needs requires understanding of the link between the mechanisms of action of novel therapeutics and specific tumor geneticts, thereby unifying molecular diagnostics and therapeutics.

Given the explosion of new information on the genetic and cellular features of malignancy and the rapidly growing armamentarium of targeted therapeutics, oncologists today must master the understanding, appreciate the significance and value the application of cancer-related basic and clinical sciences. 'This gap in knowledge and its application in clinical practice will be addressed in this conference,' Ramanathan explained.

Dr. Ramanathan is the co-program director of the conference, along with Dr. Daniel Von Hoff, TGen's Physician-In-Chief and the Chief Scientific Officer at TCRS. Both doctors conduct groundbreaking personalized-medicine research and clinical drug trials at TCRS in Scottsdale, and both are on the clinical faculty of the University of Arizona College of Medicine. Both will present at the conference.

Other TGen and Scottsdale Healthcare scientists scheduled to present include: Dr. Jeffrey Trent, TGen's President and Scientific Director; Dr. Raoul Tibes, Director of the Hematological Malignancies Program at TCRS and an Associate Investigator at TGen; Dr. Stephen P. Anthony, Chief Medical Officer of TGen Drug Development Services (TD2) and a Senior Investigator at TGen; Dr. John Carpten, Director of TGen’s Integrated Cancer Genomics Division and a Senior Investigator at TGen; and Gayle Jameson, M.S.N., Director of Supportive Care at TCRS and an Associate Investigator at TGen.

Target audience
Besides oncologists, the target audience includes all physicians and health professionals involved in caring for cancer patients, and researchers interested in new cancer diagnostics and therapeutics.

Key objectives of the conference include:

• Explaining the molecular and cellular features of malignancy in diagnostic and therapeutic approaches to the treatment of cancer, and identifying new diagnostic tools.
• Assessing the effects and early clinical results of new, targeted drug therapies on solid tumors and malignant blood cancers.
• Identifying new drug therapies that optimize treatment results and minimize side effects in specific biologic and clinical scenarios.
• Evaluating clinical trials and translational methods of care and their proper use in clinical decision-making and patient management.

The conference is sponsored by TGen, Scottsdale Healthcare's Virginia G. Piper Cancer Center and Physicians' Education Resource (PER) of Dallas. The conference is certified for Continuing Medical Education.

For more information:

• 'The Sixth Vital Sign' runs Jan. 22-24, 2009 at the Arizona Grand Resort.
• Personalized Medicine Coalition

Also read PubMed abstracts:

• Acharya CR, Hsu DS, Anders CK, Anguiano A, et al. Gene expression signatures, clinicopathological features, and individualized therapy in breast cancer. JAMA 2008 Apr 2;299(13):1574-87. Click here for a full text version of this article.
• Pene F, Courtine E, Cariou A, Mira JP. Toward theragnostics. Crit Care Med. 2009 Jan;37(1 Suppl):S50-8.

New Drug for Cancer Treatment Could Bolster Immune System

Arizona based Translational Genomics Research Institute (TGen), a non-profit organization dedicated to conducting groundbreaking medical research, together with Scottsdale Healthcare, a primary clinical research facility housed in the Virginia G. Piper Cancer Center in Scottsdale and Mayo Clinic, one of only 39 U.S. medical centres that have been named as a National Cancer Institute (NCI) Comprehensive Cancer Center, started testing VTX-2334, a novel Toll-Like Receptor 8 (TLR8) agonists for the treatment of cancer, respiratory and autoimmune diseases in early December 2008. The new drug is developed by VentiRx Pharmaceuticals, Inc., a biopharmaceutical company based in San Diego, and could help cancer patients by stimulating their immune system.

During the initial Phase I trial, a yearlong first-in-humans test, researchers will study the drug's safety and pharmacology of multiple doses of VTX-2337 in patients with late-stage cancer. If successful, a Phase II trial will test the drug's effectiveness on tumours.

Dr. Ramesh Ramanathan, Medical Director of TGen Clincal Research Services at Scottsdale Healthcare, said the new drug appears to be quite promising. ‘VTX-2337 is a new, novel, small molecule aimed at stimulating the immune cells in the blood, lymph nodes, and in and around the tumour. It represents an exciting new class of agents for cancer therapy with good preclinical evidence of activity.’

VentiRx Pharmaceuticals, founded in June 2006 by Michael Kamdar and Robert Hershberg, M.D., Ph.D, is committed to the development of novel medicines for the treatment of cancer, infectious, respiratory, and autoimmune diseases. The medical research team of experienced biotechnology professionals, is excited to be working on this new drug. Michael Kamdar, Executive Vice President and Chief Business Officer at VentiRx : ‘Entering Phase I clinical trials represents a significant milestone for VentiRx and our TLR efforts in that we have rapidly advanced into a clinical development company with a novel molecule that may play an important role and have broad application in the treatment of cancer.’

Role of the immune system
A weakened immune system is often the result of advanced cancer. 'We hope that this new drug will actually help enable the immune system to slow down the growth of tumours, and perhaps even shrink them,' Ramanathan explained.

Toll-like receptors (TLRs) play an important role in stimulating innate and adaptive immunity and TLR ligands have become interesting targets to use as stand-alone immunotherapeutics or vaccine adjuvants for cancer treatment.

VTX-2337 is a small molecule TLR8 agonist that is expected to be used in combination with standard of care for the treatment of patients with cancer. Preclinical evaluation of VTX-2337 suggests that it may play a key role in augmenting the innate arm of the immune system.
There are two broad components of the immune system, the innate arm, and the adaptive arm. Both generally aim to eliminate viruses and bacteria.

• The innate arm senses infectious agents as they infect the body by recognizing structures they have in common, such as lipids, proteins, sugars, and nucleic acids (DNA and RNA). This is an initial rapid response, which is not precise but potent.
• The adaptive arm of the immune system is instructed by the innate arm to devise more specific responses to unique components of the invading pathogens. This is a more precise response and takes longer, especially when an infectious agent is encountered for the first time.

‘VTX-2337 is the first selective TLR8 compound to reach the clinic, and we are hopeful that modulation of the innate immune response will provide a benefit to patients in a number of oncology indications,’ said Dr. Robert Hershberg, Executive Vice President and Chief Medical Officer at VentiRx.

Also read PubMed abstracts:

• Smits EL, Ponsaerts P, Berneman ZN, Van Tendeloo VF. The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy. Oncologist 2008 Aug;13(8):859-75. Epub 2008 Aug 13
• Zhang SY, Jouanguy E, Sancho-Shimizu V, von Bernuth H, et al
  Human Toll-like receptor-dependent induction of interferons in protective immunity to viruses.
  Immunol Rev 2007 Dec;220:225-36
• Uematsu S, Akira S
  Toll-like receptors and Type I interferons
  J Biol Chem 2007 May 25;282(21):15319-23. Epub 2007 Mar 29
• Ghosh TK, Mickelson DJ, Fink J, Solberg JC, et al
  Toll-like receptor (TLR) 2-9 agonists-induced cytokines and chemokines: I. Comparison with T cell receptor-induced responses.
  Cell Immunol 2006 Sep;243(1):48-57. Epub 2007 Jan 23