Navigation Links
UCLA research could enhance treatments for drug-resistant melanoma

Melanoma is the deadliest form of skin cancer, killing more than 8,000 in the U.S. each year. Approximately 40 percent of advanced melanoma tumors are driven to grow by the presence of mutations in a gene known as the BRAF gene. And although new drugs called BRAF inhibitors have shown an ability to rapidly shrink melanoma tumors, BRAF-mutated tumors often resist early treatment and only partially respond to BRAF inhibitors, which leaves behind cancer cells that can eventually grow into new tumors.

Today, two studies by researchers from UCLA's Jonsson Comprehensive Cancer Center were published online in the journal Cancer Discovery that provide critical insights into two important ways that tumors resist BRAF inhibitors. The researchers found the key cell-signaling pathways used by BRAF-mutant melanoma to learn how to become resistant to inhibitor drugs, and how the limited focus of BRAF inhibitors allows melanoma cells to evolve and become drug-resistant. The studies will appear later in the journal's print edition.

Led by Dr. Roger Lo, a member of the Jonsson Cancer Center and associate professor and director of the melanoma clinic in dermatology, the studies utilized patients' biopsy samples to give researchers powerful information that can be translated directly into the clinic. Specifically, the findings should help oncologists make better use of BRAF inhibitor drugs in combination with other drugs for melanoma patients.

In the first study, Lo and colleagues discovered how tumor cells escaped the effects of BRAF inhibitors by tracking the outgrowth of melanoma cells that had learned from different cell-signaling pathways how to become BRAF inhibitorresistant. This work, based on an analysis of 100 biopsies from patients who had been treated with BRAF inhibitors, revealed that BRAF inhibitorresistant tumors use a variety of different signaling routes to learn resistance and that people can have more than one resistance route. Clinical trials have rarely studied these phenomena at the molecular level, which Lo said provides a much more robust view of the scale and scope of the problem.

Understanding the mechanisms of tumor resistance could help doctors identify the optimal combination of inhibitor drugs to block multiple resistance routes, which eventually could shrink tumors for a much longer period, or eradicate them completely.

"By helping us understand the core resistance pathways and tumor heterogeneity, fitness and mutational patterns that emerge under drug selection, this study lays a foundation for clinical trials to investigate the mechanisms of tumor progression in BRAF-mutant melanoma patients," Lo said.

The second study, also led by Lo, found that as soon as melanomas face BRAF inhibitors they are able to quickly turn on drug resistance pathwaysa process called early adaptive resistance. Over time, these early adaptive resistance pathways are further fortified, allowing the tumor cells to break free of the BRAF inhibitor and resume growth. Therefore, early and late resistance processes are linked, and can lead to cancer recurrence and death, although the means or mechanisms may be different. Discovering the core melanoma escape pathways is an important conceptual advance when fighting BRAF inhibitor resistance, because treatments can then be designed to block these pathways all at once when treatment is initiated.

"We now have a landscape view of how melanoma first adapts and then finds ways to overcome what is initially a very effective treatment," said Dr. Antoni Ribas, a Jonsson Cancer Center member, professor of medicine and co-investigator on both studies. "We have already incorporated this knowledge into testing new combination treatments that we hope will get us back ahead of melanoma and not allow it to escape the initial treatment effectiveness and return."

Both studies were international collaborations, involving scientists from Vanderbilt University in Nashville, Tenn.; the Melanoma Institute of Australia in Sydney; and the Ludwig Institute for Cancer Research in Brussels.

The studies highlight the excellence of the translational oncology being conducted by UCLA physician-scientists, who are working to ensure that laboratory discoveries reach cancer patients as quickly as possible.


Contact: Shaun Mason
University of California - Los Angeles

Related medicine news :

1. Cincinnati Childrens researchers develop first molecular test to diagnose eosinophilic esophagitis
2. £23m to drive advances in population health sciences research
3. American Brain Tumor Association-Funded Research Spurs Development of New Treatments
4. Urinary Tract Infection Market (UTI): Gram-Negative Bacterial 2022 Epidemiology Forecasts in New Research Report at
5. US PV Devices & Accessories Market Analyzed & Forecast by iData Research in New Report Available at
6. What composes the human heart? U of T researchers crunch the numbers
7. Team of Chicago hospitals awarded grant to accelerate stroke research, treatments
8. Researcher test first-in-class compound for neuroprotection, hope of stopping MS disease progression
9. Fertility Centers of Illinois is Recruiting Patients for The MultiCenter Registry with Eeva™ (MERGE) Research Study
10. Global Animal Health Market Report 2013 Edition Research at
11. Bel Marra Health Reports on Recent Research Revealing a Link Between Intestinal Bacteria and Rheumatoid Arthritis
Post Your Comments:
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... June 19, ... the dangers associated with chronic pain and the benefits of holistic treatments, Serenity ... who are suffering with Sickle Cell Disease. , Sickle Cell Disease (SCD) is a ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Pulmonary Hypertension ... that it will receive two significant new grants to support its work to ... its 25th anniversary by recognizing patients, medical professionals and scientists for their work ...
(Date:6/24/2016)... ... June 24, 2016 , ... Dr. ... accelerated orthodontic treatment. Dr. Cheng has extensive experience with all areas of orthodontics, ... and accelerated osteogenic orthodontics. , Micro-osteoperforation is a revolutionary adjunct to orthodontic ...
(Date:6/24/2016)... ... , ... Topical BioMedics, Inc, makers of Topricin and MyPainAway Pain Relief Products, join The ‘Business ... to $12 an hour by 2020 and then adjusting it yearly to increase at the ... minimum wage, assure the wage floor does not erode again, and make future increases more ...
(Date:6/24/2016)... Norcross, Georgia (PRWEB) , ... June 24, 2016 ... ... Year” awards today at the Clinical Decision Making in Emergency Medicine conference in ... who have authored journal articles published in Emergency Medicine Practice and ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 24, 2016 Research and ... "Structural Electronics 2015-2025: Applications, Technologies, Forecasts" report ... In-Mold Electronics, Smart Skin, Structural Health Monitoring, ... Structural electronics involves electronic and/or electrical components ... replacing dumb structures such as vehicle bodies or ...
(Date:6/24/2016)... 2016 According to a new ... Pen Needles, Safety Pen Needles), Needle Length (4mm, 5mm, ... Mode of Purchase (Retail, Non-Retail) - Trends & Global ... the market for the forecast period of 2016 to ... Billion by 2021 from USD 1.65 Billion in 2016, ...
(Date:6/23/2016)... Research and Markets has announced the ... to 2022" report to their offering. ... patients with kidney failure, it replaces the function of kidneys ... blood and thus the treatment helps to keep the patient ... Increasing number of ESRD patients & substantial ...
Breaking Medicine Technology: