PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Sanford-Burnham researchers identify a new target for treating drug-resistant melanoma

Study explains why some melanoma tumors are resistant to BRAF inhibitor treatment

2015-05-28
(Press-News.org) La Jolla, Calif., May 28, 2015 - A new collaborative study led by researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham), published today in Cell Reports, provides new insight into the molecular changes that lead to resistance to a commonly prescribed group of drugs called BRAF inhibitors. The findings suggest that targeting newly discovered pathways could be an effective approach to improving the clinical outcome of patients with BRAF inhibitor-resistant melanoma tumors.

Melanoma is the deadliest form of skin cancer, killing more than 8,000 people in the U.S. each year. Approximately 50 percent of melanoma tumors are driven by mutations in the BRAF gene, and patients with these tumors are prescribed BRAF inhibitors. Although BRAF inhibitors rapidly and effectively shrink tumors, their success is limited because most tumors become resistant to the drugs within a few months.

"Melanoma tumors can develop resistance to BRAF inhibitors by using alternate signaling pathways that promote cell growth," said Ze'ev Ronai, Ph.D., scientific director of Sanford-Burnham's La Jolla campus and senior author of the study. "Our study has identified a different pathway, JAK1, as a driver of resistance to BRAF inhibitors, and suggests that targeting JAK1 could overcome such resistance, thereby improving the durability of the response to BRAF inhibitors."

How it works The research team analyzed BRAF inhibitor resistance in melanoma cell lines, mice bearing human melanoma tumors, and in human tumor biopsy samples. They found higher levels of JAK1 in resistant tumors, which caused increased expression of epidermal growth factor (EGFR)--a receptor tyrosine kinase that promotes cell proliferation. The increase in JAK1 was due to low levels of the protein that regulates its expression, ubiquitin ligase RNF125.

JAK1 is part of a well-studied regulatory network of proteins that is involved in the control of cell growth, differentiation, apoptosis, inflammation, and immune response. Until know, JAK1 was not known to play a role in melanoma or its resistance to therapy.

"By helping us understand that lower levels of RNF125 confer resistance to BRAF inhibitors, we have a new strategy to stratify patients for currently approved therapy versus participation for human clinical trials to investigate whether targeting JAK1 will be more effective in patients whose tumors exhibit reduced RNF125," said Keith T. Flaherty, M.D., associate professor, Harvard Medical School, and director of Developmental Therapeutics, Cancer Center, Massachusetts General Hospital, and co-author of the study. "It will be important to determine whether JAK1 therapy alone or in combination with EGFR and BRAF inhibitors will elicit a better response."

INFORMATION:

The study was an international collaboration involving scientists from Massachusetts General Hospital (Harvard University) Mass.; University of Zurich, Switzerland; the University of Texas MD Anderson Cancer Center, Texas; the National Cancer Institute, Md.; and Yale School of Medicine, Conn.

This study was funded by NIH grant CA128814, and by grants from the Melanoma Research Foundation and the Hervey Family Non-endowment Fund at the San Diego Foundation.

ABOUT SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham takes a collaborative approach to medical research with major programs in cancer, neurodegeneration and stem cells, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is recognized for its National Cancer Institute-designated Cancer Center, its NIH-designated Neuroscience Center Cores, and expertise in drug discovery technologies. Sanford-Burnham is a nonprofit, independent institute that employs more than 1,000 scientists and staff in San Diego (La Jolla), Calif., and Orlando (Lake Nona), Fla. For more information, visit us at sanfordburnham.org.

Sanford-Burnham can also be found on Facebook at facebook.com/sanfordburnham and on Twitter @sanfordburnham.



ELSE PRESS RELEASES FROM THIS DATE:

Sleep quality influences the cognitive performance of autistic and neurotypical children

Sleep quality influences the cognitive performance of autistic and neurotypical children
2015-05-28
This news release is available in French. One night of poor sleep significantly decreases performance on intelligence tests in children with autism spectrum disorder (ASD) and also in neurotypical children (without ASD). This is the conclusion made by researchers at the Hôpital Rivière-des-Prairies, affiliated with the Institut universitaire en santé mentale de Montréal and Université de Montréal. For a paper published in the International Journal of Psychophysiology, the researchers observed the EEG measures of 13 autistic children ...

Health factors influence ex-prisoners' chances of returning to jail

2015-05-28
Ex-prisoners with a history of risky drug use, mental illness or poverty are more likely to end up back behind bars. Those who are obese, are chronically ill or have attempted suicide are more likely to remain in the community. These are some of the findings from an exploratory study into health-related factors that could be used to predict whether a person released from prison will end up in custody again. It was led by Emma Thomas of the University of Melbourne in Australia and is published in Springer's journal Health & Justice, an open access journal. In many countries, ...

Public raises alarm about ineffectiveness of some Montagu's harrier conservation measures

Public raises alarm about ineffectiveness of some Montagus harrier conservation measures
2015-05-28
A citizen science programme reveals the protection measures for the Montagu's harrier in the cereal crop season in France to be ineffective if nests are not protected to decrease predation after harvesting. A study has been published as a result of this voluntary fieldwork, with the participation of the Hunting Resources Research Institute, which proposes fencing off the nests as a way of mitigating the damage and optimising conservation efforts in different areas. Over the last decade there has been an explosion in the so-called citizen science programmes, in which people ...

In battle of the sexes, a single night with a New York male is enough to kill

In battle of the sexes, a single night with a New York male is enough to kill
2015-05-28
EUGENE, Ore. -- (May 28, 2015) -- Men and women often enter relationships with different long-term goals. In the animal world, differences in approaches to reproductive success can lead to sexual conflict. Male fruit flies, for example, transfer proteins during mating that can alter the timing of a female's egg laying and her tendency to later mate with other males. Some of these male-derived proteins also migrate from the female's reproductive tract to her brain. Now, in a new study, scientists of the University of Oregon and Bowdoin College show that sexual conflicts ...

Research roundup from Penn's Abramson Cancer Center

2015-05-28
CHICAGO -- Researchers from the Abramson Cancer Center of the University of Pennsylvania and Penn's Perelman School of Medicine will present results from several clinical trials and other key studies during the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting from May 29 through June 2. Results of Phase II Trial Show Successful Antitumor Response Rate in Patients with Advanced BRCA-Related Ovarian Cancer Olaparib, an experimental twice-daily oral cancer drug, produces significant antitumor responses in more than a third of patients with BRCA-related ...

Peek eye testing app shown to work as well as charts for visual acuity

2015-05-28
An app to test eyesight easily and affordably using a smartphone is as accurate as traditional charts, according to a study published today. Peek (the Portable Eye Examination Kit) is a unique smartphone-based system for comprehensive eye testing anywhere in the world which has been designed and developed by the London School of Hygiene & Tropical Medicine, the University of Strathclyde and the NHS Glasgow Centre for Ophthalmic Research. Globally, 285 million people are visually impaired and 80% have diseases which could be cured or prevented. However, most live in ...

Estimating the global burden of cancer in 2013; 14.9 million new cases worldwide

2015-05-28
Researchers from around the world have worked together to try to measure the global burden of cancer and they estimate there were 14.9 million new cases of cancer, 8.2 million deaths and 196.3 million years of a healthy life lost in 2013, according to a Special Communication published online by JAMA Oncology. The Global Burden of Disease study by the Global Burden of Disease Cancer Collaboration group provides a comprehensive assessment of new cancer cases (incidence), and cancer-related death and disability. Researchers relied on cancer registries, vital records, verbal ...

Metformin use associated with reduced risk of developing open-angle glaucoma

2015-05-28
Taking the medication metformin hydrochloride was associated with reduced risk of developing the sight-threatening disease open-angle glaucoma in people with diabetes, according to a study published online by JAMA Ophthalmology. Medications that mimic caloric restriction such as metformin can reduce the risk of some late age-onset disease. It is unknown whether these caloric mimetic drugs affect the risk of age-associated eye diseases such as macular degeneration, diabetic retinopathy, cataract or glaucoma. Researcher Julia E. Richards, Ph.D., of the University of ...

Hearing impairment higher among Hispanic/Latino men, older individuals

2015-05-28
Hearing impairment was more prevalent among men and older individuals in a study of U.S. Hispanic/Latino adults, according to a report published online by JAMA Otolaryngology-Head and Neck Surgery. Hearing impairment is a common chronic condition that affects adults. Hearing impairment may lead to lower quality of life and is associated with an increased risk for dementia. Most hearing impairment is undiagnosed and untreated. Karen J. Cruickshanks, Ph.D., of the University of Wisconsin, Madison, and co-authors determined the prevalence of hearing impairment among Hispanic/Latino ...

Nearly 1 in 7 Hispanic/Latino adults has some hearing loss

2015-05-28
This news release is available in Spanish. In the largest study to date of hearing loss among Hispanic/Latino adults in the United States, researchers have found that nearly 1 in 7 has hearing loss, a number similar to the general population prevalence. The analysis also looked at the differences between subgroups and found that Hispanics of Puerto Rican descent have the highest rate of hearing loss, while Mexican-Americans have the lowest. The study identified several potential risk factors for hearing loss, including age, gender, education level, income, noise exposure, ...

LAST 30 PRESS RELEASES:

‘Molecular shield’ placed in the nose may soon treat common hay fever trigger

Beetles under climate stress lay larger male eggs: Wolbachia infection drives adaptive reproduction strategy in response to rising temperature and CO₂

Groundbreaking quantum study puts wave-particle duality to work

Weekly injection could be life changing for Parkinson’s patients

Toxic metals linked to impaired growth in infants in Guatemala

Being consistently physically active in adulthood linked to 30–40% lower risk of death

Nerve pain drug gabapentin linked to increased dementia, cognitive impairment risks

Children’s social care involvement common to nearly third of UK mums who died during perinatal period

‘Support, not judgement’: Study explores links between children’s social care involvement and maternal deaths

Ethnic minority and poorer children more likely to die in intensive care

Major progress in fertility preservation after treatment for cancer of the lymphatic system

Fewer complications after additional ultrasound in pregnant women who feel less fetal movement

Environmental impact of common pesticides seriously underestimated

The Milky Way could be teeming with more satellite galaxies than previously thought

New study reveals surprising reproductive secrets of a cricket-hunting parasitoid fly

Media Tip Sheet: Symposia at ESA2025

NSF CAREER Award will power UVA engineer’s research to improve drug purification

Tiny parasitoid flies show how early-life competition shapes adult success

New coating for glass promises energy-saving windows

Green spaces boost children’s cognitive skills and strengthen family well-being

Ancient trees dying faster than expected in Eastern Oregon

Study findings help hone precision of proven CVD risk tool

Most patients with advanced melanoma who received pre-surgical immunotherapy remain alive and disease free four years later

Introducing BioEmu: A generative AI Model that enables high-speed and accurate prediction of protein structural ensembles

Replacing mutated microglia with healthy microglia halts progression of genetic neurological disease in mice and humans

New research shows how tropical plants manage rival insect tenants by giving them separate ‘flats’

Condo-style living helps keep the peace inside these ant plants

Climate change action could dramatically limit rising UK heatwave deaths

Annual heat-related deaths projected to increase significantly due to climate and population change

Researchers discover new way cells protect themselves from damage

[Press-News.org] Sanford-Burnham researchers identify a new target for treating drug-resistant melanoma
Study explains why some melanoma tumors are resistant to BRAF inhibitor treatment