skin cancer Archives - Sanford Burnham Prebys

Tag: skin cancer

Institute News

Skincare safety in the sunshine state

AuthorDeborah Robison
Date

June 14, 2017

happy retired senior couple sitting on the beach holding hands and enjoying summer vacations

Current melanoma incidence in older white men (65 and older) is about five times that of the general population.

Before age 50, the incidence of melanoma in women is higher than men but by age 65, melanoma incidence rates are twice as high in men. By ages 80 and older, the rate is three times higher in men than women of the same age.

Why are older men highly susceptible to melanoma? Over a lifetime, men spend more time outdoors accumulating ultraviolet exposure and are less diligent about wearing sun protection. They may also be less likely to perform skin self-exams and have physician check-ups. Also, research shows that melanoma may advance differently in men than women and that men’s tumors may grow more rapidly.

Prevention through early detection of melanoma is especially important in reducing mortality in high-risk groups – older men being the largest high-risk group of all. Part of the reason for the high mortality rate is the difficulty in distinguishing benign skin moles from malignant melanomas.

Ranjan Perera, PhD, associate professor at Sanford Burnham Prebys Medical Discovery Institute at Lake Nona pinpoints the problem:  “Current tests are inconclusive at least 15 percent of the time, requiring repeated biopsies.” His lab is researching new biomarkers that could provide clinicians with earlier and more reliable diagnostics for melanoma. His approach focuses on micro-RNAs (non-protein coding genetic material) that may contribute to the formation and progression of melanoma.  

Research suggests that the majority of melanomas – nearly 90 percent – are considered to be preventable, so following guidelines to limit exposure to damaging UV (ultraviolet) sunlight is the first line of defense.  Severe sunburns, especially during childhood, increase your risk of developing melanoma and other skin cancer. Just one blistering sunburn can double your chances of developing melanoma later in life.

Perera and collaborator Michael Steppie, MD, assistant professor of dermatology at Florida State University, are investigating various skin disorders. Dr. Steppie, a noted Florida dermatologist, offers these sun safety suggestions for people who live in warm weather regions.  

Follow these tips to reduce your risk of developing melanoma.

  • Remember that all skin types can develop skin cancer including people who tan easily or have naturally dark skin.
  • Generously apply sunscreen to all exposed skin — even on cloudy days — year-round.
  • Use a sunscreen that provides broad spectrum protection from both UVA and UVB rays and has a sun protection factor (SPF) of at least 30 SPF.
  • Apply approximately one ounce of sunscreen (a shot-glassful) 15 minutes before sun exposure.
  • Reapply sunscreen every two hours and after swimming or sweating.
  • Keep newborns out of the sun. Sunscreens should be used on babies over the age of six months.
  • Wear a long-sleeved shirt, pants, a wide-brimmed hat (preferably sun-protective clothing, accessories and swimwear carrying a UPF 50+ label) and UV-Blocking sunglasses.
  • Seek shade when possible. The sun’s rays are the strongest between 10 a.m. and 4 p.m.
  • Water, snow and sand reflect and magnify the damaging rays of the sun, increasing your chance of sunburn. Especially during peak hours while at the beach, stay in the shade from an umbrella carrying a UPF 50+.
  • Avoid tanning beds – there is no way to get a tan through UV exposure without increasing the risk for skin cancer. Using a tanning bed before age 35 increases your risk for melanoma by 75 percent.
  • Be aware that certain prescription medications and over-the-counter drugs can increase your skin’s sensitivity to sunlight
  • Sun-proof your car windows with UVA-filtering window glass or film.

Source: Melanoma Research Foundation, American Academy of Dermatology

Institute News

What SBP Scientists are Researching to Battle Skin Cancer

AuthorHelen I. Hwang
Date

May 16, 2017

Nevus sample from Peter D. Adams' lab

Skin cancer is one of the most common of all cancers, and melanoma accounts for about 1 percent of skin cancers. However, melanoma causes a large majority of deaths from that particular type of cancer. Alarmingly, rates of skin cancer have been on the rise in the last 30 years. Here in Southern California, our everlasting summer comes with a price. Exposure to sun increases our risk to melanoma. 

Melanoma occurs when the pigment-producing cells that give color to the skin become cancerous. Symptoms might include a new, unusual growth or a change in an existing mole. Melanomas can occur anywhere on the body. 

At Sanford Burnham Prebys Medical Discovery Institute (SBP), we have several researchers working on the causes of melanoma and discovering new ways to treat this deadly disease.

 

Here is a roundup of SBP’s latest research

Key findings show how melanoma develops in order to identify potential therapeutic targets

Ze’ev Ronai, PhD
Professor and SBP Chief Scientific Advisor

Ronai’s laboratory has been studying how rewired signaling networks can underlie melanoma development, including resistance to therapy and metastatic propensity. One player in that rewiring is a protein called ATF-2, which can switch from its usual tumor-preventive function to become a tumor promoter when combined with a mutation in the human gene called BRAF.

Ronai’s work on a protein, ubiquitin ligases, led to the identification of RNF125 as an important regulator of melanoma resistance to a common chemotherapy drug. RNF125 impacts melanoma resistance by its regulation of JAK2, an important protein kinase which could play an important role in melanoma resistance to therapy. 

Work on the ubiquitin ligase Siah2 identified its important role in melanoma growth and metastasis, and its contribution to melanomagenesis. Melanoma is believed to be a multi-step process (melanomagenesis) of genetic mutations that increase cell proliferation, differentiation, and death. 

Work in the lab also concern novel metabolic pathways that are exploited by melanoma for their survival, with the goal of identifying combination drug therapies to combat the spread of melanoma. Earlier work on the enzyme PDK1 showed how it can be a potential therapeutic target for melanoma treatment.
 

Immunotherapy discovery has led to partnership with Eli Lilly

Linda Bradley, PhD
Professor, Immunity and Pathogenesis Program, Infectious and Inflammatory Diseases Center

Bradley’s group is focused on understanding how anti-tumor T cells can be optimized to kill melanoma tumors. They discovered an important molecule (PSGL-1) that puts the “break” on killer T cells, allowing melanoma tumors to survive and grow. Using animal models, they removed this “break” and T cells were able to destroy melanoma tumors. They have extended their studies and found that in melanoma tumors from patients, T cells also have this PSGL-1 “break”. Bradley’s lab has partnered with Eli Lilly to discover drugs that can modulate PSGL-1 activity in human disease that may offer new therapies for patients.

Knocking out a specific protein can slow melanoma growth 

William Stallcup, PhD
Professor, Tumor Microenvironment and Cancer Immunology Program

The danger of melanomas is their metastasis to organs, such as the brain, in which surgical removal is not effective. By injecting melanoma cells into the brains of mice, we have shown that the NG2 protein found in host tissues makes the brain a much “friendlier” environment for melanoma growth. 

Specifically, NG2 is found on blood vessel cells called pericytes and on immune cells called macrophages. The presence of NG2 on both cell types improves the formation of blood vessels in brain melanomas, contributing to delivery of nutrients and thus to accelerated tumor growth. Genetically knocking out NG2 in either pericytes or macrophages greatly impairs blood vessel development and slows melanoma growth.

 

Mysterious molecule’s function in skin cancer identified

Ranjan Perera, PhD
Associate Professor, Integrative Metabolism Program

Ranjan’s research uncovered the workings of a mysterious molecule called SPRIGHTLY that has been previously implicated in colorectal cancer, breast cancer and melanoma. These findings bolster the case for exploring SPRIGHTLY as a potential therapeutic target or a biological marker that identifies cancer or predicts disease prognosis.

 

Drug discovery to help babies has led to a clinical trial at a children’s hospital

Peter D. Adams, PhD
Professor, Tumor Initiation and Maintenance Program

Approximately 1 in 4 cases of melanoma begins with a mole, or nevus. Genetic mutations can cause cells to grow uncontrollably. By investigating how this occurs, we can understand why melanoma develops from some moles, but not others.

Babies born with a giant nevus that covers a large part of the body have especially high risk of melanoma, and the nevus cells can spread into their spine and brain. Adams’ research identified a drug that deters the cells from growing. The drug identified will be used in a clinical trial at Great Ormond Street Children’s Hospital in London, England that may help babies with this debilitating disease.  

 

Discovery of a receptor mutation correlates with longer patient survival

Elena Pasquale, PhD
Professor, Tumor Initiation and Maintenance Program

Pasquale’s work has included whether mutations in the Eph receptor, tyrosine kinases, play a role in melanoma malignancy. Eph receptor mutations occur in approximately half of metastatic melanomas. We found that some melanoma mutations can drastically affect the signaling ability of Eph receptors, but could not detect any obvious effects of the mutations on melanoma cell malignancy. 

Bioinformatic analysis of metastatic melanoma samples showed that Eph receptor mutations correlate with longer overall patient survival. In contrast, high expression of some Eph receptors correlates with decreased overall patient survival, suggesting that Eph receptor signaling can promote malignancy. 

Institute News

Super-oncogenic protein that promotes development of melanoma

AuthorJessica Moore
Date

May 19, 2016

Header image

An international collaborative study led by scientists at the Sanford Burnham Prebys Medical Discovery Institute (SBP) has identified a malicious form of a protein that drives the formation of melanoma. The findings, published in Cell Reports, reveal unexpected insight into how this lethal skin cancer develops and progresses, and may help understand and develop novel therapies against these aggressive tumors.

“We found that an inactive version of a protein called activating transcription factor 2 (ATF2) elicits a tumor-promoting effect in a way not seen before,” said Ze’ev Ronai, PhD, chief scientific advisor of SBP and professor of its NCI-designated Cancer Center. “We have known for years that the active version of ATF2 promotes melanoma, but this result was a surprise because we thought ATF2 transcriptional activity was essential to activate cancer-related genes.”

Ronai’s team has been studying ATF2’s role in melanoma for two decades. Their past work led to the view that it’s dangerous when it’s in the nucleus because it controls cancer-enabling genes, but benign when it’s not.

In the current study, researchers looked at the oncogenic potential of a ‘dead’ form of ATF2 in mice with mutations in BRAF, a kinase that transmits signals promoting cell division and is often mutated in pigmented skin cells. The same mutation is found in about half of all human melanomas.

“Inactive ATF2, in mice with mutant BRAF, resulted in the formation of pigmented lesions and later, melanoma tumors,” said Ronai, senior author of the study.

“What makes this discovery relevant to human melanoma is that we identified a structurally similar form of inactive ATF2 in human melanoma samples that has the same effects on cancer cells,” added Ronai. “Inactive ATF2 could be an indicator of tumor aggressiveness in patients with BRAF mutations, and maybe other types of cancer as well.”

“Unlike models with more complex genetic changes, like the inactivation of PTEN and p16 combined with BRAF mutations that result in rapid tumorigenesis (within a few weeks), the inactive ATF2 caused BRAF mutant mice to develop melanoma much slower, more similar to the timescale seen in patients,” commented Ronai. “This improves our ability to monitor the development of melanoma and efficacy of possible interventions.”

“We’re now investigating why inactive ATF2 so potently promotes BRAF-mutant melanoma, and looking for other types of cancer where it acts the same way,” Ronai said. “Our findings may guide precision therapies for tumors with mutant ATF2.”

The paper is available online here.

Institute News

A sugar found in seaweed may help treat skin cancer

Authorsgammon
Date

December 8, 2015

Header image

New research from scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) suggests that a rare sugar found in seaweed, mushrooms, seeds and other foods may be able to help treat skin cancer. The sugar, called L-fucose, has previously been linked to a number of pathological conditions including inflammation and certain cancers. The current study, published in Science Signaling, is the first to associate L-fucose with melanoma, the most dangerous form of skin cancer.

“Our findings offer new, unprecedented detail into the sugar’s role in cancer,” said Ze’ev Ronai, PhD, senior author and scientific director of SBP’s La Jolla campus. “We found that by tampering with L-fucose metabolism, we could inhibit melanoma tumor metastasis. Not only were the tumors affected but also their microenvironment—the cells surrounding the tumor that play a critical role in sustaining the cancer—making the discovery even more impactful.”

Sugars, such as glucose and sucrose, come from many different sources and are used by the body in unique ways. Some sugars, including L-fucose, provide crucial tags on cell-surface proteins that signal inflammation and help direct cell migration. Previous research has shown that changes in the amount of L-fucose on cells are associated with breast and stomach cancers.

The study started with a broader investigation of activating transcription factor 2 (ATF2), a protein that controls the expression of many other proteins and that has been implicated in the development of melanoma and other cancers. Ronai’s group has been studying ATF2 for more than 20 years.

“To our surprise, one of the genes found to be regulated by ATF2 was fucokinase (FUK), which controls the ability of cells to process the dietary sugar, L-fucose, into a form that is useable for the modification (fucosylation) of proteins, many of which are on the cell surface, said Ronai.”

“In human samples, we found reduced fucosylation in metastatic melanomas and a better prognosis for primary melanomas with increased fucosylation. We suspect that the absence of L-fucose on melanoma cells makes them less sticky and more mobile in the body, making them more likely to metastasize,” Ronai explained.

Importantly, in mice with melanoma, the researchers were able to increase fucosylation either by adding the sugar to their drinking water or by genetic manipulation. Both methods inhibited the growth and metastasis of the tumors.

“Many patients develop resistance to current melanoma drugs. If we can add something like L-fucose to enhance these therapies, that’s very exciting, and it’s something we’re actively looking into,” said lead author Eric Lau, PhD, who is extending studies on the role of L-fucose in melanoma at the H. Lee Moffitt Cancer Center in Tampa, Florida,

“The dietary result was especially gratifying, because it suggests that modifying fucosylation could be achieved by the simple addition of L-fucose to drinking water.

“Our results further suggest that the addition of dietary sugar may help fight melanoma by boosting numbers of helpful immune cells. We are continuing our exploration of how fucosylation and other sugar coatings affect the immune system and impact cancer,” added Ronai.

To read the paper click here