The Significance of Translational Research (Part 2)

Translational Research

Translational research accelerates the transfer of scientific knowledge into practical applications, leading to advancements in medicine and healthcare. By translating discoveries into clinical practice, researchers can address unmet medical needs, develop new treatments, and improve existing therapies.

Continue reading

Other Gene Tests for Cancer

Other than the BRCA1 and BRCA2 gene mutation test for breast and ovarian cancer, there are other gene-related tests available for cancer.

As an example, one such test that is available is for Lynch syndrome, a hereditary condition which comes with a family history of colon cancer and other types of cancer at a younger age. Those with the syndrome have a higher risk of colorectal and uterine (womb) cancers.

Like BRCA screening, the genetic screening test for Lynch is expensive and is recommended only for high-risk individuals with a strong family history of such cancers.

Trying to find the Lynch syndrome in the general population would be rather costly and not necessarily helpful, said Dr Lim Sheow Lei, a senior consultant at the department of gynaecological oncology at KK Women’s and Children’s Hospital.

BLOG CTA ButtonRead more about how targeted treatments and translational science research methods are creating better outcomes for patients with cancer

The field of cancer genetics is a rapidly evolving area.?? But things are changing quickly.? As genomic technology advances, the cost of sequencing the human genome is plunging, said Dr Lim. Just two weeks ago, a US company announced it was offering a much cheaper and easier way for women to get tested for the BRCA1 and BRCA2 genetic mutations.

Color Genomics* has begun selling a test (USD $249) that it said could accurately analyze a saliva sample for the mutations, as well as check for 17 other genetic variants that have been associated with a somewhat increased risk for cancer of the breast or ovaries.

Cancer can sometimes appear to “run in families” even if it is not caused by an inherited mutation.? Acquired mutations are the most common cause of cancer. These mutations occur from genes damaged during a person’s life. Smoking, viruses, and aging can damage genes and cause these mutations.

One such cancer caused by an acquired mutation is cervical cancFREE MS Art - Cancer Biology Ribboner, which stem from the human papilloma virus (HPV). Last year, the US Food and Drug Administration approved the HPV DNA test, manufactured by Roche, as a first-line primary screening test in women 25 and older. The geno-typing test detects DNA from 14 high-risk HPV types and specifically identifies HPV 16 and HPV 18, which carry the highest risk of cervical cancer. It can be used to help a healthcare professional assess the need for the woman to undergo additional diagnostic testing for cervical cancer. The test can also provide information about the patient’s risk for developing cervical cancer in the future.

Women who test positive for HPV 16 or HPV 18 should have a colposcopy, an examination using a device that illuminates and magnifies the cervix so a doctor can directly observe the cervical cells. Those who test positive for one or more of the 12 other high-risk HPV types should have a PAP smear to determine the need for a colposcopy. In a United States study of more than 47,000 women that compared HPV DNA tests with PAP smear tests, up to one in three women with cervical cancer had a normal PAP smear result.

Scientists and researchers are uncovering more genetic markers for other cancers.? The challenge is to know what to do with these pieces of information, how to interpret the multitude of newly uncovered mutations, work out the associated cancer risks and to manage the risks, said Dr Lim.

(Reprinted with license and permission from The Straits Times by Ng Wan Ching)
RePubHub Banner

 

Got Questions? We have Answers! Contact us at CriteriumBlog@criteriuminc.com

*Information and link for Color Genomics does not constitute our endorsement of or any liability associated with the product, company or service.? Please consult a physician in case you believe you or someone you know may have cancer.

The Top 5 Recent Breakthroughs in Advanced Lung Cancer Treatment

Ross Camidge MD PHD ATOMICWe might need to look at our back catalogues for treatments we could retrospectively explore for effective predictive biomarkers with our more modern approaches. ?D. Ross Camidge, MD, PhD

A countdown of the top 5 breakthrough therapies in the treatment of advanced lung cancer was presented by D. Ross Camidge, MD, PhD, at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. Dr. Camidge is Director, Thoracic Oncology Clinical and Clinical Research Programs, and Associate Director for Clinical Research, University of Colorado Comprehensive Cancer Center, Aurora. He is also the Director for the newly minted ATOMIC Lung Cancer Consortium. He chose the following molecular therapies as his top choices for illustrating what the future of Lung cancer treatment will involve:

#5. Crizotinib

Dr. Camidge chose crizotinib(Xalkori) as a breakthrough therapy ?because of how it has exemplified the philosophy of one size does not fit all,? he said.

#4. Second-Generation ALK Inhibitors

The second-generation ALK inhibitors werechosen ?not because of their impressive activity post-crizotinib, but because of their progress in accurately defining how we capture data on benefit in central nervous system (CNS) disease,? Dr. Camidge explained.

#3. Third-Generation EGFR Inhibitors

Dr. Camidge identified the third-generation EGFR inhibitors ?because of what they are teaching us about understanding acquired resistance in order to effectively treat it,? he said.

#2. PD-1/PD-L1 Antagonists

Dr. Camidge singled out the inhibitors of programmed death receptor 1 (PD-1) and its ligand (PD-L1) as opening the door to immunotherapy but with the open question of whether they will really be a panacea or whether they have the potential to become a truly personalized medicine.

#1. Three Possible Future Breakthroughs

The?number 1 spot was shared by three ?mini-fantasies? about what future breakthroughs might be, based on the concepts of mining the past, intraoncogene heterogeneity, and affordable incremental benefit.

Explaining his interest in mining the past, Dr. Camidge said, ?We have walked away from a large number of targeted agents because they didn?t work when given to otherwise unselected lung cancer populations. However, in almost all of these cases, no attempt at robustly exploring predictive biomarkers was conducted,? he noted.

?Consequently, the classes of drugs may not truly be ineffective, and there may have been evidence of hypersensitive subpopulations ripe for re-exploration,? he continued. ?We might need to look at our back catalogues for treatments we could retrospectively explore for effective predictive biomarkers with our more modern approaches.?

As an example, he cited the class of drugs known as death receptor agonists. These drugs ?which directly stimulate apoptosis and worked exceptionally well in various preclinical models, were all dropped when a series of randomized phase II studies adding these agents to first-line chemotherapy failed to show an advantage.? But the nonprogressors in the experimental arms approached 15% of the population in several of the studies, he said. ?Unfortunately little or no tissue was collected in these studies so no predictive biomarkers could really be explored at the time.?

Dr. Camidge used KRAS as an example of intraoncogene heterogeneity. The most common mutation among adenocarcinomas of the lung, KRAS has been shown in preclinical and clinical studies to have tremendous heterogeneity. The trial design for the FAK inhibitor VS-6063 in KRAS-mutant lung cancer is ?at least starting to address this heterogeneity by exploring its benefit in four KRAS-mutant cohorts that have also been characterized with regard to their INK4a and p53 status to see if these contexts alter the response to the drug, based on relevant preclinical data,? Dr. Camidge said.

To explain affordable incremental benefit, he cited the REVEL study, which looked at the addition of ramucirumab (Cyramza), an antibody against VEGFR2, to standard second-line docetaxel. ?The addition of ramucirumab increased the response rate from 14% to 30% and the disease control rate from 53% to 64%, increased the progression free survival from 3.0 to 4.5 months, and increased the overall survival from 9.1 to 10.5 months,? Dr. Camidge reported.

?So with an unequivocally positive phase III study, adding a little to all major endpoints, we might want to be using this drug. But only if it, and drugs like it, are affordable, as one recurring problem has been in pricing a breakthrough as if it?s a game-changer and not just a way of offering a little incremental benefit to everyone.? If not affordable, ?these minor breakthroughs will never be practical to use in the real world,? he said.

Disclosures: Dr. Camidge has received honoraria from Pfizer, Genentech/Roche, Clovis, Aria, and Eli Lilly.

Reference
Camidge DR: The top five most promising molecular therapies on the horizon. Chicago Multidisciplinary Symposium in Thoracic Oncology. Presented October 31, 2014.

Source/Complete article by Charlotte Bath (The ASCO Post) is available at: http://www.ascopost.com/issues/december-1,-2014/top-5-breakthroughs-in-the-treatment-of-advanced-lung-cancer.aspx

Got Questions? We have Answers! Contact us at CriteriumBlog@criteriuminc.com