Breaking News
August 15, 2018 - Cardiac Profiles Up With Exercise, Less Sitting in Early Old Age
August 15, 2018 - Precision medicine offers a glimmer of hope for Alzheimer’s disease
August 15, 2018 - Immunovia’s new blood-based testing platform accurately detects non-small cell lung cancer
August 15, 2018 - New method provides a ‘big picture’ of genetic influences on traits and diseases
August 15, 2018 - Early Onset Type 1 Diabetes Linked to Heart Disease, Shorter Life
August 14, 2018 - SMURF1 provides targeted approach to preventing cocaine addiction relapse
August 14, 2018 - Genetic testing pushed for hereditary high cholesterol disease
August 14, 2018 - Researchers discover new genes involved in Alzheimer’s Disease
August 14, 2018 - Medicare to overhaul ACOs but critics fear fewer participants
August 14, 2018 - Adolescent health projects receive meager percentage of global funding, study finds
August 14, 2018 - University Hospitals Seidman Cancer Center launches new CAR-T therapy trial
August 14, 2018 - In the addiction battle, is forced rehab the solution?
August 14, 2018 - Busting myths about milk – Scope
August 14, 2018 - Platelet-rich plasma does not enhance cartilage formation capabilities of stem cells
August 14, 2018 - Wearable devices and ‘mhealth’ technology emerge as promising tools for better health
August 14, 2018 - Clinical study suggests new treatment direction for head and neck cancer in heavy smokers
August 14, 2018 - Phase 2 Clinical Data Published Showing Summit’s Ridinilazole Preserved Gut Microbiome of Patients with CDI
August 14, 2018 - Cardiac progenitor cells undergo a cell fate switch to build coronary arteries
August 14, 2018 - Study identifies potential guidance to treat gastric cancer patients
August 14, 2018 - Revealed: The molecular mechanism underlying hypertrophic cardiomyopathy, or “workaholic heart”
August 14, 2018 - Diabetes epidemic in Guatemala driven by aging, not obesity
August 14, 2018 - New technology shows potential to streamline the analysis of proteins
August 14, 2018 - Rethinking the stroke rule ‘time is brain’
August 14, 2018 - Incidence of coronary artery compression in children may be more common than previously thought
August 14, 2018 - Study helps to better understand disease caused by Alpha-1 antitrypsin deficiency
August 14, 2018 - AI platform identifies acute neurological illnesses faster than human diagnosis
August 14, 2018 - American College of Rheumatology receives grants to support development of lupus clinical trials
August 14, 2018 - New study explains why women get more migraines than men
August 14, 2018 - American Heart Association Urges Screen Time Limits for Youth
August 14, 2018 - Brief interventions during routine care reduce alcohol use among men with HIV
August 14, 2018 - New genome analysis could identify people at higher risk of common deadly diseases
August 14, 2018 - NIH grant for Mount Sinai to study use of inhaled corticosteroids for treatment of sickle cell disease
August 14, 2018 - Daicel supplies free nanodiamond samples to international researchers
August 14, 2018 - Switching anti-psychotic drugs in first-episode schizophrenia patients does not improve clinical outcomes
August 14, 2018 - Study to examine whether modulating gut bacteria can improve cardiac function in heart failure patients
August 14, 2018 - AI technology could hold key to improving health services
August 14, 2018 - One out of two children not getting enough nutrients needed for their health
August 14, 2018 - Mono-antiplatelet therapy after aortic heart valve replacements may work as well as two drugs
August 14, 2018 - Aid-in-dying patient chooses his last day
August 14, 2018 - Exercise Really Can Chase Away the Blues, to a Point
August 14, 2018 - Surgical mesh implants may cause autoimmune disorders
August 14, 2018 - Researchers develop revolutionary zebrafish model to gain more insight into bone diseases
August 14, 2018 - Researchers discover secret communication hotline between breast cancers and normal cells
August 14, 2018 - Study examines how a person adapts to visual field loss after stroke
August 14, 2018 - Researchers show how specialized nucleic acid-based nanostructures could help target cancer cells
August 14, 2018 - Reducing opioid prescriptions for one operation can also spill over to other procedures
August 14, 2018 - E-cigarettes not so safe but still better than cigarettes
August 14, 2018 - Researchers find link between common ‘harmless’ virus and cardiovascular damage
August 14, 2018 - Initiation of PIMs associated with higher risk of fracture-specific hospitalizations and mortality
August 14, 2018 - Genetically modified mosquitoes and special bed nets help tackle deadly diseases
August 14, 2018 - Advances in treating hep C lead to new option for transplant patients
August 14, 2018 - Study finds quality of doctor-patient discussions about lung cancer screening to be ‘poor’
August 14, 2018 - MSU researchers uncover the effects of aging on regenerative ability of kidneys
August 14, 2018 - Better conditioning, throwing mechanics can help reduce elbow injuries in young baseball pitchers
August 14, 2018 - Brain game doesn’t offer brain gain
August 14, 2018 - Reproductive choices facing women with disabilities require careful consideration
August 14, 2018 - Scientists pinpoint the cause of a rare childhood seizure disorder
August 14, 2018 - Lumpectomy plus radiation associated with reduced risk of breast cancer death, study finds
August 14, 2018 - UAB study shows how ion channel differentiates newborn and mature neurons in the brain
August 14, 2018 - Experts highlight key knowledge gaps that need to be addressed in Ebola vaccine research
August 14, 2018 - Discovery could lead to new drugs against infection and inflammation
August 14, 2018 - Infection Prevention Differs Between Small, Large Hospitals
August 14, 2018 - Mom still matters—In study, young adults tended to prioritize parents over friends
August 14, 2018 - Deep brain stimulation might benefit those with severe alcoholism, preliminary studies show
August 14, 2018 - Study finds increased rate of repeat pregnancies in women with intellectual and developmental disabilities
August 14, 2018 - Lighter sedation fails to reduce risk of postoperative delirium in older patients
August 13, 2018 - Asking better questions about person’s memory could improve doctors’ understanding of patients
August 13, 2018 - U.S. Trauma Doctors Push for Stricter Gun Controls
August 13, 2018 - Asthma and flu: a double whammy
August 13, 2018 - 5 Questions: Donna Zulman on engaging high-need patients in intensive outpatient programs | News Center
August 13, 2018 - Behavioral Nudges Lead to Drop in Prescriptions of Potent Antipsychotic
August 13, 2018 - Potential New Class of Drugs May Reduce Cardiovascular Risk by Targeting Gut Microbes
August 13, 2018 - How to get your kids to eat better
August 13, 2018 - The importance of hearing your patients
August 13, 2018 - Transmission of F. tularensis unlikely to happen through the food chain
August 13, 2018 - Researchers discover epigenetic mechanism underlying ischemic cardiomyopathy
August 13, 2018 - Adolescent health programs receive only a tiny share of international aid, finds research
August 13, 2018 - Fracture risk increases by 30% after gastric bypass, study shows
August 13, 2018 - Quality-improvement project to standardize feeding practices helps micro preemies gain weight
August 13, 2018 - Long-term cannabinoid exposure impairs memory, study shows
Penn scientists identify new therapeutic target for treatment of melanoma

Penn scientists identify new therapeutic target for treatment of melanoma

image_pdfDownload PDFimage_print

Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous pregnancy with better outcomes after a melanoma diagnosis. Now, a research team from Perelman School of Medicine at the University of Pennsylvania says it may have determined the reason for the melanoma-protective effect. The mechanism is related to a cellular protein called the G protein-coupled estrogen receptor (GPER). When GPER was activated and combined with anti PD-1inhibitor drugs in mouse cancer models, the therapy dramatically extended survival in all animals and completely eliminated the tumor in 50 percent of the mice. Researchers published their findings in the journal eLife today.

Melanoma is the deadliest form of skin cancer, despite accounting for only about one percent of skin cancers overall. Rates of melanoma have been rising for 30 years, and the American Cancer Society estimates there were more than 87,000 new cases in the United States in 2017. Even with recent advances in immunotherapy, the majority of patients with metastatic forms of melanoma will die from their disease.

“In melanoma and many other types of cancer, women have a better prognosis than men, and women with a history of pregnancy seem to have a better prognosis than those women that have never been pregnant” said the study’s senior author Todd W. Ridky, MD, PhD, an assistant professor of Dermatology at Penn. “Decades of research certainly suggests that there is something about female sex and pregnancy hormones that helps protect against melanoma, but no one really understood how that might work.”

Researchers say the key is GPER, a receptor found on melanocytes, which are pigment-producing cells in the skin. The receptor is normally activated by estrogen, which is higher in females, especially during pregnancy. Activation of GPER likely explains why many women notice that many areas of their skin gets darker during pregnancy. Previous research from the Ridky lab has shown the effects of GPER activation are totally different than the effects of classical estrogen receptor signaling, which is important in breast cancer. The team discovered that melanocytes do not even express the classical estrogen receptor, and that all estrogen effects were the result of GPER.

In melanoma specifically, once GPER is activated, the cancer cell becomes more differentiated. This means it divides less frequently, makes more pigment, and becomes more visible and vulnerable to the natural immune system. This makes it harder for the cancer to become resistant to immunotherapies.

No drugs specifically target GPER, but Ridky and his team used a lab compound called G-1, originally developed by Eric Prossnitz, PhD, at the University of New Mexico Comprehensive Cancer Center, to stimulate GPER in mice, and then used anti-PD-1 inhibitors to treat the melanoma. The approach eliminated the tumors in half of all mice. The authors note that anti-PD-1 inhibitors, when used alone in mice with melanoma, extend survival modestly, but do not completely eliminate tumors, and no animals survive long-term.

“We hope this work inspires other researchers to revisit old ideas of differentiation-based cancer therapies now that immune therapies are available,” said the study’s lead author Christopher A. Natale, a researcher in Ridky’s lab. “It is clear that the future of cancer therapy lies in combination treatments, and differentiation drivers may be a very useful component in future cancer therapy regimens.”

As Ridky points out, this represents a unique approach to immunotherapy and cancer therapy in general.

“So much of the cancer field is focused on inhibitors, but in this new treatment approach, we’re actually activating something rather than blocking it,” Ridky said. “We used a synthetic compound to mimic part of what happens naturally during pregnancy, and as a result, the GPER activator is very well tolerated without any obvious toxic side effects that are common with most cancer drugs.”

Ridky also said this approach could be promising beyond melanoma.

“This is a receptor that is expressed in many organs, so there’s a reasonable expectation that this may work in other tumor types too,” Ridky said.

Although researchers did not observe any toxicities from the compound in mice, though they say they plan further toxicity studies before hopefully moving on to human trials.

Source:

https://www.med.upenn.edu/

Tagged with:

About author

Related Articles