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Friday, July 21, 2017

Offering financial incentives to patients eligible for a preventive colonoscopy screening more than doubled the rate of screening when compared to a simple emailed request, according to new research from the Perelman School of Medicine at the University of Pennsylvania.

Screening colonoscopies improve the chance of early detection and prevention of colorectal cancer, but tens of millions of Americans who should have preventive screenings fail to get them. The new study suggests that a simple financial incentive may be able to persuade many of those holdouts to undergo this important medical procedure (Gastroenterology 2017; doi:10.1053/j.gastro.2017.07.015)."Colonoscopy is challenging for patients, requiring a day off from work, a bowel cleansing preparation, and transportation, in addition to non-financial costs of anxiety and discomfort," said lead author Shivan J. Mehta, MD, an Assistant Professor of Medicine at the Perelman School of Medicine and Associate Chief Innovation Officer at Penn Medicine, Philadelphia. "The improvement we saw in the rate of screening colonoscopies was statistically significant, and shows for the first time that a financial incentive can at least modestly boost that rate."

Colorectal cancers kill more than 50,000 people in the US every year - second only to lung cancers - despite the fact that the vast majority of potential colorectal tumors can be detected via colonoscopy and removed easily, usually at the precancerous stage. The USPSTF has recommended screening colonoscopies every 10 years until the age of 75, for most healthy adults starting at age 50, and for adults with a strong family history of colorectal cancer starting earlier. Studies suggest that from one-third to more than one-half of eligible people fail to get screening colonoscopies.

The new study included 2,245 people between 50 and 64 years old. Following a behavioral economics technique called active choice, Mehta and colleagues sent an email to one subset of participants asking that they actively opt in or opt out of a screening colonoscopy. To another subset, the researchers sent an email with the same active choice message plus an inducement of $100 cash for a colonoscopy completed within 3 months. To a third group, the control group, the researchers sent an email with just a phone number for scheduling a screening colonoscopy.

Only 1.6 percent of the control group and 1.5 percent of the simple active choice group ended up receiving a screening colonoscopy within 3 months, compared to 3.7 percent of the group that was offered the $100 inducement. The rate of appointment scheduling was also more than double in the $100-inducement group (4.8%) compared to the control and active choice groups (2.1% and 2.0%, respectively).

Providing people with financial incentives to adopt healthier behaviors, or follow medical guidelines is already becoming a standard practice among insurers and employers. Such incentives have been proven effective in some cases, for example in persuading people to cut back on smoking, to take their medications, and to lose weight.

Researchers have found it harder to persuade people to undergo colorectal cancer screening. For example, the Affordable Care Act of 2009 eliminated patient cost sharing for colonoscopies and other colorectal cancer screening procedures - up to a $500 value for some people - but did not lead to a wider adoption of these procedures.

The effectiveness of the inducement used in this study, he suggested, may have come from the relatively large amount of money offered as a cash reward, and the fact that it was offered along with easy access to scheduling for the procedure.

"Although a $100 incentive seems relatively large, this amount is comparable to what employers already offer for completion of health risk assessments or biometric screening activities," noted Mehta, who also works with teams in Penn's Center for Health Incentives and Behavioral Economics and the Center for Health Care Innovation, to lead research looking at how health care systems can leverage behavioral economics, care redesign, and information technology to improve population health. "Based on the results, the approach could be applied by employers or insurers to improve existing efforts to reduce the burden of colorectal cancer."

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Wednesday, July 19, 2017

The gene p53 functions normally as a cancer suppressor, but mutated versions of the gene have been implicated in the development and growth of nearly half of all human cancers. Scientists at VCU Massey Cancer Center, Richmond, Va., have uncovered a mechanism that makes lung cancer cells dependent on mutated versions of the gene, opening the potential for new, more effective treatments (J Clin Invest 2017;127(5):1839-1855).

Each year, lung cancer kills more people than colon, breast, and prostate cancers combined. The American Cancer Society estimates there will be more than 220,000 new cases of lung cancer in the U.S. in 2017, further underscoring the need for new, more effective therapies.

Swati Palit Deb, PhD, a member of the Cancer Molecular Genetics research program at Massey and an Associate Professor in the Department of Biochemistry and Molecular Biology at the VCU School of Medicine, led a team of scientists to reveal a strategy to prevent the growth of lung cancer in cultured cell lines as well as mouse models by blocking the function of the surveillance protein, ChK1, needed to increase the success of genome duplication.

"Some mutated versions of p53, known as gain of function mutations, not only loose tumor suppressor functions, but also gain oncogenic functions. This is the first time that anyone has shown a mechanism by which cancer cells depend on gain of function mutations of the p53 gene for survival and growth," said Deb. "With this knowledge, we may be able to develop new therapies that kill lung cancer cells with gain of function p53 mutations while sparing healthy tissue."

At the heart of the researchers' discoveries is the process of genome duplication during cell growth. All cells progress through a cycle that leads to DNA replication and cellular division, and each phase of that cycle is responsible for preparing for and completing genome duplication and cell division that results in two new copies of the cell. By studying the cancer cells' genomes, researchers showed that mutated p53 genes produce excess ChK1 and cyclin A proteins. These proteins help regulate progression through the cell cycle, and ChK1, in particular, helps prevent the collapse replication forks.

"Inhibitors of ChK1 have been used to prevent cancer cell growth in experiments and have progressed to clinical trials with limited success," noted Deb. "The new information from our studies is that the ChK1 inhibitors should specifically be effective in stopping cancer cell multiplication in patients with gain-of-function p53 mutations. Thus, we feel ChK1 inhibitors have not been used for the right group of cancer patients.

"We plan to develop strategies that utilize these findings to block the spread of lung cancers with mutated p53," she concluded. "And because p53 is mutated in a majority of other cancers, our findings could help inform the development of new treatments for many different cancer types."​


Wednesday, July 19, 2017

Scientists have discovered a new type of immune cell that could predict which lung cancer patients will benefit most from immunotherapy treatment, according to a study recently published in Nature Immunotherapy (2017; doi:10.1038/ni.3775).

Researchers at the University of Southampton and La Jolla Institute for Allergy & Immunology, California, found that lung cancer patients with large amounts of a particular type of immune T cell, called tissue-resident memory T cells, in their tumor were 34 percent less likely to die.

The study also found that it was not just the number of cells that increased survival, but the cells' behavior played a key role. The cells clustered together and "took up residency" in a particular tissue, in this case the cancer tissue, to protect the patient.

These new T cells also produce other molecules that attack the tumor, which suggests the body's immune system could be more likely to hunt out and destroy cancer cells.

Immunotherapies have shown great promise in the past decade, but identifying which patients respond to treatment and which don't has proven difficult. In the future, testing for levels of these cells could help doctors identify which patients will benefit most from immunotherapies that help to ramp up the body's attack on the cancer.

Scientists could take this one step further by using the T cell as a template to develop a vaccine to boost immunotherapy even more—helping tackle one of the hardest-to-treat cancers.

"These are hugely exciting results. For the first time, we have a real indication of who might benefit from a particular drug before we make treatment decisions. So far, when we use immunotherapy, we do not know if a patient will benefit. The new findings are a big step towards making this exciting treatment much more predictable," said Professor Christian Ottensmeier, MD, PhD, FRCP, Cancer Research UK scientist at the University of Southampton.

"Our results will also make the treatment pathway more reassuring for our patients. And if we can translate our finding into clinical practice, then we will also save patients unnecessary side effects and reduce costs."​


Wednesday, July 19, 2017

A new study is set to improve treatment options for patients with the second most common type of lung cancer, squamous cell carcinoma, a disease for which new anti-cancer drugs are urgently needed.

The researchers demonstrated a better way to recruit the right participants for fibroblast growth factor receptor (FGFR) inhibitors, which are being investigated for treating lung squamous cell carcinoma.

Using a research tool that mimics the complexity of human tumor, the researchers identified a biomarker that would better categorize the patients who would respond to the treatment. They also showed that combining the targeted FGFR inhibitors with chemotherapy had the potential to improve treatment outcomes.

Walter and Eliza Hall Institute researchers Marie-Liesse Asselin-Labat, PhD, Clare Weeden, PhD, and Aliaksei Holik, PhD, worked closely with medical oncologist Professor Ben Solomon, MBBS, PhD, FRACP, and Richard Young from the Peter MacCallum Cancer Centre on the study (Mol Cancer Ther 2017; doi:10.1158/1535-7163.MCT-17-0174).

Asselin-Labat said the teams discovered a better biomarker for identifying those lung cancer patients who were most likely to respond to FGFR inhibitors. "We found that high levels of the anti-cancer drug's target—FGFR1—in a patient's tumor RNA were a better predictor of their potential response to the drug than the current tests that are used."

Solomon noted that the finding could improve the design of future clinical trials by selecting the right patients to participate. "Fewer than 10 percent of new cancer drugs make it past phase I clinical trials. In many cases, this isn't because of the drug itself, but because of a limitation in clinical trial design.

"Understanding which patients are most likely to respond to certain drugs in clinical trials is crucial both for patients to receive the best treatment, and for new drugs to make it to the clinic," he continued. "Hopefully these data will help to improve trial outcomes by recruiting patients who otherwise might not have been matched to the right trial for them."

In addition to identifying which patients would respond to the targeted therapy, the study found that FGFR inhibitors could be turbo-charged when combined with chemotherapy, according to Weeden.

"FGFR inhibitors stop cancer cells from growing and adding in chemotherapy kills the cancer," she said. "Our research shows combining FGFR inhibitors with chemotherapy should be looked at in future clinical trials."

Additionally, Weeden said lung cancer tissue samples donated to the Victorian Cancer Biobank by patients were key to the research. "Our laboratory models—known as patient-derived xenografts —are the most accurate representation of real patient tumors that can be used for testing."

"These models, using samples donated to the biobank by people with lung cancer, were crucial to define which tumors responded best to FGFR inhibitors," she added.

The researchers hope to apply their findings to other forms of non-small cell lung cancer, which together account for 85 percent of people with lung cancer, Asselin-Labat said. "This research is a great example of the benefits of collaboration between basic scientists and clinical specialists," she concluded.​


Wednesday, July 12, 2017

Many potent anti-cancer drugs have major drawbacks -- they fail to mix with water, which means they will have a limited solubility in blood, and they lack selectivity to cancer cells.

Researchers at the University of Alabama, Birmingham, and Texas Tech University Health Sciences Center, Lubbock, have developed micro-cubes that can sponge up a hydrophobic anti-cancer drug and deliver it to cancer cells. Tissue culture tests show these tiny, porous cubes, loaded with the hydrophobic drug, are more potent against liver cancer cells and less harmful to normal liver cells, compared to the drug alone.

"We believe that our novel drug-delivery platform for the highly potent anti-cancer drug BA-TPQ provides a facile method for encapsulation of hydrophobic drugs and can facilitate enhanced efficacy for liver cancer therapy," noted the researchers (Acta Biomater 2017; doi: 10.1016/j.actbio.2017.06.004).. The liver cancer, hepatocellular carcinoma, is the third-leading cause of cancer death worldwide, and the need for new curative compounds that can improve patient outcomes is urgent.

BA-TPQ is an iminoquinone derivative, and it is one of the most potent analogs of natural anti-cancer compounds discovered in the Philippine sponge Zyzzya fuliginosa.

BA-TPQ has high potency against human breast and prostate cancer cell lines, but its use has been limited by poor solubility, low bioavailability, and undesirable toxicity. The goals for a delivery system are improved anti-cancer efficacy and reduction of side effects.

The research was led by co-senior authors Eugenia Kharlampieva, PhD, and Sadanandan E. Velu, PhD, both Associate Professors of Chemistry in the UAB College of Arts and Sciences; and Ruiwen Zhang, MD, PhD, Professor in the School of Pharmacy, Texas Tech University Health Sciences Center.

The 2-micrometer cubes are made of layers of cross-linked poly(methacrylic acid) formed on a porous scaffold that is then removed. Poly(methacrylic acid) is non-toxic and is biocompatible for clinical use.

The hydrogel carriers filled with BA-TPQ are soft but can retain their cubic shape, and the cubic shape aids uptake by cancer cells. A higher redox potential, such as that found inside cells, facilitates dissolution of the tiny cubes and release of the BA-TPQ drug. Furthermore, cancer cells often have higher redox potentials than normal cells.

The drug-loaded cubes can be freeze-dried and then re-suspended in solution without losing their shape, which may allow long-term storage of the cubes as a powder.

Besides the selectivity of the BA-TPQ-hydrogel cubes for the two lines of liver cancer cells tested in comparison with normal liver cells, the drug-loaded cubes affected the expression of genes involved in cancer promotion or prevention.​