Contact Information:

Media Contact

Vanessa Wasta
wasta@jhmi.edu
410-614-2916

Twitter: HopkinsMedicine

http://www.hopkinsmedicine.org




Kredyty mieszkaniowe Kredyty mieszkaniowe

Sprawdź aktualny ranking najlepszych kredytów mieszkaniowych w Polsce - atrakcyjne kredytowanie nieruchomości.

PRESS-NEWS.org - Press Release Distribution
FREE PRESS RELEASES DISTRIBUTION
RSS - Press News Release
Add Press Release

Genetic biomarker may predict cancer patients' response to immunotherapy drug

Researchers caution that larger studies are needed to assess the potential for clinical use


2015-05-29
(Press-News.org) In a report of a proof-of-principle study of patients with colon and other cancers for whom standard therapies failed, researchers at the Johns Hopkins Kimmel Cancer Center say that mistakes in so-called mismatch repair genes, first identified by Johns Hopkins and other scientists two decades ago, may accurately predict who will respond to certain immunotherapy drugs known as PD-1 inhibitors. Such drugs aim to disarm systems developed by cancer cells to evade detection and destruction by immune system cells.

Results of the trial with pembrolizumab, marketed as Keytruda, will be presented at the American Society of Clinical Oncology 2015 Annual Meeting and published online May 30 in the New England Journal of Medicine.

"This study gives us a solid clue about how immunotherapy may work in cancer and how to guide immunotherapy treatment decisions based on the genetic signatures of a cancer rather than class of cells or organ of origin," says Luis Diaz Jr., M.D., an oncologist at the Johns Hopkins Kimmel Cancer Center, a member of the Ludwig Center at Johns Hopkins and the director of the Swim Across America Laboratory at Johns Hopkins.

"Defects in mismatch repair genes are found in a small percentage of many cancer types, and this type of biomarker for immunotherapy response could apply to tumors containing errors in other DNA repair genes, as well," says Dung Le, M.D., an oncologist at the Johns Hopkins Kimmel Cancer Center. "Using a predictive biomarker can help us direct the use of immunotherapy drugs to patients who are more likely to respond, avoiding giving people expensive and time-consuming treatments that are not likely to work or delaying the use of other treatments."

For the Johns Hopkins-led study, scientists enrolled and treated 48 patients with cancer, primarily at The Johns Hopkins Hospital, and divided them into three groups. Other patients enrolled were from Providence Cancer Center in Oregon, the University of Pittsburgh Cancer Institute, Stanford University and The Ohio State University Comprehensive Cancer Center.

In one group of 13 patients with advanced colon and rectal cancers and mismatch repair gene defects, eight had partial responses to pembrolizumab, meaning their cancers shrunk by at least 30 percent in diameter. Four patients had prolonged disease stability, and one patient experienced disease progression. In another group of patients with colon and rectal cancer who had no defects in mismatch repair genes, all 25 failed to respond. In a third group of 10 patients with a variety of other cancers that tested positive for mismatch repair gene defects (four with pancreatic/bile duct cancers, two with uterine cancers, two with small bowel cancers, one with stomach cancer and one with prostate cancer), one patient with uterine cancer had a complete response, meaning there was no radiographic evidence of their cancer, five had partial responses, one had stable disease and three patients' cancers progressed.

All patients had received and were no longer responding to previous therapies.

"It's rare for patients with colon cancer who have failed all standard therapies to respond and most of them only have a few months to live," says Kenneth W. Kinzler, Ph.D., co-director of the Ludwig Center at Johns Hopkins. "While it's promising to see that patients with mistakes in mismatch repair genes responded more often to immunotherapy than those who did not have these mistakes, we need to test this idea in more patients and potentially earlier on in the sequence of therapies for these advanced cancers."

Median overall and disease progression-free survival in the colon cancer group with mismatch repair-defect group have not been reached yet, since several patients in this group have continued to respond to the immunotherapy drug for more than 12 months. Median follow-up for this group is 36 weeks (ranging from five to 55 weeks). In the group of patients with colon cancer who lack the mismatch repair errors, median overall survival was 7.6 months, and median disease progression was 2.3 months. These patients were followed for up to 42 weeks. In the third group of patients with mistakes in mismatch repair genes, median overall survival has not been reached, and their median disease progression-free survival was 5.4 months after being followed for up to 42 weeks.

For the study, overall response rates and some disease progression-free survival rates were classified and assessed as "immune-related," because patients often experience some tumor growth before shrinkage begins in those who respond. Typically, such initial tumor growth, also known as pseudo-progression, would prompt researchers to remove patients from a clinical trial, but scientists have recognized the temporary growth trend in immunotherapy trials and created new definitions of response to account for it, say the Johns Hopkins scientists.

The research team also accounted for differences in how long each patient had metastatic disease and his or her length of response to previous therapies.

Tests for mistakes in mismatch repair genes are commercially available and used routinely for newly diagnosed colon and endometrial cancer patients, according to Le. Pembrolizumab, sold by Merck, is approved by the Food and Drug Administration for certain patients with melanoma. The drug blocks a protein on immune cells called PD-1 and takes the brakes off of these immune cells so they can attack cancer cells.

Its cost can reach more than $100,000 per year per patient, a cost that gives urgency to sorting out which patients stand to benefit and which do not.

Mistakes in mismatch repair genes, which occur in sporadic and hereditary forms of colorectal, endometrial, stomach, biliary tract, pancreas, ovarian and small intestine cancer, disable cells' ability to repair errors in the DNA replication process, which triggers unchecked cellular growth, a hallmark of cancer. The mutations were first identified in 1993 by co-authors of the current study, including Bert Vogelstein, M.D., of the Ludwig Center at Johns Hopkins and an investigator for the Howard Hughes Medical Institute; Nickolas Papadopoulos, Ph.D., and Kenneth Kinzler, Ph.D., also of Johns Hopkins' Ludwig Center; and Albert de la Chapelle at Ohio State University.

Two decades later, an idea for the current study took root when Diaz and his Ludwig Center colleagues met with other Johns Hopkins scientists who led one of the first large clinical trials of a type of immunotherapy similar to the one used in the current study. In it, a single patient with colon cancer in the trial responded to the drug when other patients with colon cancer did not. The search began, Diaz says, for why that one patient responded.

Diaz and his colleagues previously proposed that immunotherapy may work best in patients with more mutations in their cancer cells, because multiple mutations trigger production of more abnormal proteins in cancer cells and, in turn, may cause the immune system to mount a bigger response against cancer cells with more "foreign" proteins. Knowing that a small percentage of patients with colon cancer have errors in mismatch repair genes, which produce thousands more mutations in tumors than patients without the defects, they guessed that the lone colon cancer responder in the earlier study had such error-prone mismatch repair genes, a guess that was subsequently verified when the team sequenced the genome of the patient's tumor.

INFORMATION:

Funding for the study was provided by the cancer philanthropy Swim Across America, the Lustgarten Foundation for Pancreatic Cancer Research, the Banyan Gate Foundation, the Commonwealth Fund, the Sol Goldman Pancreatic Cancer Research Center, and the National Institutes of Health's National Cancer Institute (P50CA062924, CA163672, CA43460, CA67941, CA16058 and CA57345).

Other scientists involved in the study include Jennifer Uram, Bjarne Bartlett, Holly Kemberling, Aleksandra Eyring, Andrew Skora, Brandon Luber, Nilofer Azad, Dan Laheru, Barbara Biedrzycki, Ross Donehower, Atif Zaheer, Feriyl Bhaijee, Thomas Heubner, Ralph Hruban, Laura Wood, Nathan Cuka, Drew Pardoll, Shibin Zhou, Toby Cornish, Janis Taube, Bob Anders, and James Eshleman from Johns Hopkins; George Fisher from Stanford; Todd Crocenzi from the Providence Cancer Center; James Lee from the University of Pittsburgh; Steven Duffy from Bon Secours Cancer Institute; Richard Goldberg from Ohio State; and Minori Koshiji from Merck Inc. Diaz, Kinzler, Vogelstein, Papadopoulos and Zhou are co-founders of Personal Genome Diagnostics and PapGene. Diaz, Vogelstein, Kinzler, Papadopoulos and Zhou own stocks in Personal Genome Diagnostics, which did the genome sequencing involved in this study. Kinzler, Vogelstein and Papadopoulos are consultants to Sysmex Inostics. PapGene, Personal Genome Diagnostics and Sysmex Inostics have licensed several patent applications from Johns Hopkins. These relationships are subject to certain restrictions under The Johns Hopkins University policy, and the terms of these arrangements are managed by the university in accordance with its conflict-of-interest policies. Vogelstein, Kinzler, Papadopoulos and Le have a patent pending on technology involved in the study.

Media Contacts: Vanessa Wasta, 410-614-2916, wasta@jhmi.edu Amy Mone, 410-614-2915, amone@jhmi.edu


ELSE PRESS RELEASES FROM THIS DATE:

Modeling storm surge to better protect Texas

2015-05-29
The recent floods in Texas have caused some of the worst flooding since Hurricane Ike in 2008, causing the rainiest month in the state's history. What lessons have been learned from Ike's devastation of the Galveston and Houston area, and how have they helped in the prediction of future such storms? Researchers at the Institute for Computational Engineering and Sciences at the University of Texas at Austin have been studying computational models and simulations of hurricanes like Ike in order to predict the consequences of such natural disasters and better prepare ...

Newer, easier to manage medications may not always be the best choice

2015-05-29
PHOENIX -- If you are over age 75, and taking an anticoagulant, the old standard may be the gold standard, Mayo Clinic researchers and collaborators have determined. In a study released online in April in the BMJ, a team of researchers from Mayo Clinic, and other collaborators, showed that for older patients, particularly individuals greater than 75 years of age, the risk of gastrointestinal (GI) bleeding is 3 to 5 times higher when taking newer anticoagulant medications dabigatran or rivaroxaban compared to when using warfarin. One of the most common reasons people ...

The Large Synoptic Survey Telescope: Unlocking the secrets of dark matter and dark energy

The Large Synoptic Survey Telescope: Unlocking the secrets of dark matter and dark energy
2015-05-29
At a traditional stone-laying ceremony outside La Serena, Chile on April 14th, construction officially began of the Large Synoptic Survey Telescope (LSST). This ambitious international astrophysics project is slated to start scanning the heavens in 2022. When it does, LSST should open up the "dark universe" of dark matter and dark energy--the unseen substance and force, respectively, composing 95 percent of the universe's mass and energy--as never before. On April 2, 2015, the Director of LSST, Steven Kahn, along with astrophysicist Sarah Bridle and theoretical physicist ...

Alzheimer's culprit causes memory loss even before brain degeneration

2015-05-29
The study, published May 29 in the open access Nature Publishing Group journal Scientific Reports, reveals a direct link between the main culprit of Alzheimer's disease and memory loss. Alzheimer's disease is characterized by the formation of amyloid plaques in the brain tissue. These amyloid plaques are made up of an insoluble protein, 'Amyloid-beta' (Abeta), which forms small structures called 'oligomers' that are important in the disease progression. Although these proteins are known to be involved in Alzheimer's, little is understood about how they lead to memory ...

New 'designer carbon' from Stanford boosts battery performance

New designer carbon from Stanford boosts battery performance
2015-05-29
Stanford University scientists have created a new carbon material that significantly boosts the performance of energy-storage technologies. Their results are featured on the cover of the journal ACS Central Science. "We have developed a 'designer carbon' that is both versatile and controllable," said Zhenan Bao, the senior author of the study and a professor of chemical engineering at Stanford. "Our study shows that this material has exceptional energy-storage capacity, enabling unprecedented performance in lithium-sulfur batteries and supercapacitors." According to ...

Experts on aging: UN Sustainable Development Goals discriminatory, ageist

2015-05-29
One of the main health targets proposed by the UN Sustainable Development Goals (SDG) is to reduce by one-third premature mortality from non-communicable diseases such as cancer, stroke and dementia. The goals for 2016-2030 define premature mortality as deaths occurring among people aged 69 years old or younger. The proposed SDG target sends an unambiguous statement to UN member states that health provision for younger groups must be prioritised at the expense of people aged 70 or more, according to the international group of signatories of the letter published in The ...

Prosthetic hands with a sense of touch? Breakthroughs in providing 'sensory feedback' from artificial limbs

2015-05-29
May 29, 2015 - Researchers are exploring new approaches to designing prosthetic hands capable of providing "sensory feedback." Advances toward developing prostheses with a sense of touch are presented in a special topic article in the June issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS). Emerging sensory feedback techniques will provide some sensation and enable more natural, intuitive use of hand prostheses, according to the review by ASPS Member Surgeon Paul S. Cederna, MD, of University ...

Migraine surgery for teens -- good results in initial experience

2015-05-29
May 29, 2015 - As in adults, migraine surgery is effective for selected adolescent patients with severe migraine headaches that don't respond to standard treatments, reports a study in the June issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS). ASPS Member Surgeon Bahman Guyuron, MD, Emeritus professor of plastic surgery at Case School of Medicine, Cleveland, and colleagues report good outcomes in an initial experience with migraine surgery in younger patients. They write, "Our data demonstrate ...

Altered pain processing in patients with cognitive impairment

2015-05-29
May 29, 2015 - People with dementia and other forms of cognitive impairment (CI) have altered responses to pain, with many conditions associated with increased pain sensitivity, concludes a research review in PAIN®, the official publication of the International Association for the Study of Pain. The journal is published by Wolters Kluwer. The available evidence questions the previous notion that people with CI have reduced pain sensitivity to pain. Rather, "It appears that those with widespread brain atrophy or neural degeneration...all show increased pain responses ...

CWRU social work researchers create easier, accurate way to analyze TSCC trauma results

2015-05-29
The 54-question Trauma Symptoms Checklist for Children (TSCC) has been used for decades to test how trauma affects youth in hopes of developing the best treatment and support possible. But interpreting the results can be labor intensive and difficult because the work is done manually and involves a complex matrix from which to draw conclusions. Now, a Case Western Reserve University social work research team, led by Fredrick Butcher, PhD, a research associate at the Semi J. and Ruth W. Begun Center for Violence Prevention Research and Education, has proposed and tested ...

LAST 30 PRESS RELEASES:

How your brain decides blame and punishment -- and how it can be changed

Uniquely human brain region enables punishment decisions

Pinpointing punishment

Chapman University publishes research on attractiveness and mating

E-cigarettes: Special issue from Nicotine & Tobacco Research

Placental problems in early pregnancy associated with 5-fold increased risk of OB & fetal disorders

UT study: Invasive brood parasites a threat to native bird species

Criminals acquire guns through social connections

Restoring ocean health

Report: Cancer remains leading cause of death in US Hispanics

Twin study suggests genetic factors contribute to insomnia in adults

To be fragrant or not: Why do some male hairstreak butterflies lack scent organs?

International team discovers natural defense against HIV

Bolivian biodiversity observatory takes its first steps

Choice of college major influences lifetime earnings more than simply getting a degree

Dominant strain of drug-resistant MRSA decreases in hospitals, but persists in community

Synthetic biology needs robust safety mechanisms before real world application

US defense agencies increase investment in federal synthetic biology research

Robots help to map England's only deep-water Marine Conservation Zone

Mayo researchers identify protein -- may predict who will respond to PD-1 immunotherapy for melanoma

How much water do US fracking operations really use?

New approach to mammograms could improve reliability

The influence of citizen science grows despite some resistance

Unlocking secrets of how fossils form

What happens on the molecular level when smog gets into the lungs?

Using ultrasound to clean medical instruments

Platinum and iron oxide working together get the job done

Tiny silica particles could be used to repair damaged teeth, research shows

A quantum lab for everyone

No way? Charity's logo may influence perception of food in package

[Press-News.org] Genetic biomarker may predict cancer patients' response to immunotherapy drug
Researchers caution that larger studies are needed to assess the potential for clinical use
Press-News.org is a service of DragonFly Company. All Rights Reserved.
Issuers of news releases are solely responsible for the accuracy of their content.