New drug shows promise in the fight against malignant melanoma

September 29, 2009 By Melissa Beattie-Moss
New drug shows promise in the fight against malignant melanoma

(PhysOrg.com) -- Gavin Robertson is not a man who uses the word ‘hate’ lightly, but he makes no secret of his desire to slay the dragon that is malignant melanoma.

"This is the deadliest form of ," he said. "There’s an approximately four percent increase per year in new cases and no effective treatment available for metastatic disease. The worst thing is getting calls from patients and their families who are desperate for a cure, for some good news. It’s so hard telling them we’re not there yet."

Robertson -- associate professor of pharmacology, pathology, dermatology and surgery at the Penn State College of Medicine -- has new reason to believe that hopeful treatment news is ahead.

Tests in mice suggest that the new drug he and colleagues have developed is both safer and more potent than conventional therapies in targeting melanoma tumors. Based on the anti-cancer compounds in cruciferous vegetables, the new drug called isoselenocyanate "got a 60 to 70 percent response rate in mice," said Robertson. "That’s significant."

For Robertson and his research team, including professor of pharmacology Shantu Amin, the goal has been to unravel the signaling pathways involved in tumor development and identify drugs to target them.

In all life forms -- from single-celled to multi-cellular humans -- cells communicate with each other through chemicals, such as hormones and neurotransmitters. Protein molecules on the surfaces of cells, called receptors, recognize these incoming chemical messages, and, when all goes right, they react by initiating the requested change in some aspect of , from activating the immune system to fight infection to turning a fertilized egg into a fully-formed baby.

However, things don’t always go right. Sometimes when complex sequences of proteins are activated, a new ‘abnormally active ’ is created, and researchers believe that communication glitches in these pathways can give rise to cell changes and ultimately to cancer.

"We set out to target the proteins that trigger melanoma," Robertson said. "Ninety percent of normal skin moles contain a mutant protein called B-Raf, but don’t proceed to become melanomas. We wanted to know why some do and how to turn off that mechanism."

Robertson and colleagues discovered that in about 70 percent of melanoma tumors there is another protein at work alongside B-Raf called Akt3, which is 10 times more active in malignant cells than in normal ones.

For cancer to start, the activity in the B-Raf pathway has to be in a particular narrow range, said Robertson.

"When this pathway is too active, it actually inhibits cancer and a mole develops that does not become cancerous. But when the A protein, Akt3, holds hands with the B protein, the B-Raf, and transfers information to it, it adds a phosphate to the mix and the pathway activity then drops into just the right range, and melanoma develops."

Knowing that you’d have to eat "impractical amounts" of cruciferous vegetables such as cabbage and kale to obtain a therapeutic level of their cancer-fighting nutrients, sulforaphane and selenium, Robertson and colleagues sought to develop a drug using these nutrients that could deactivate the Akt3 pathway.

"We modified the chemical structure, increased the carbon chain length to make it more soluble, then popped out the sulfur and replaced it with selenium," said Robertson. "We knew from studies that selenium deficiency is common in cancer patients, and selenium has also been shown to destabilize Akt proteins in prostate cancer."

The result?

"When we tried the sulfur version, it had no effect on the melanoma tumors in mice," Robertson said, "but when we used the selenium version of the drug, up to 70 percent of the mice showed tumor regression." The selenium-enhanced compounds "significantly reduced the production of Akt3 protein and shut down its signaling network."

Though still years away from human trials, Robertson envisions a drug that could be used intravenously by melanoma patients, as well as preventively in sunscreen by the general public (some of the research on topical applications was done by Hershey high school senior Natalie Nguyen, an intern in Robertson’s lab. Nguyen’s project took third place in the 2009 Intel International Science and Engineering Fair).

"I think we’re finally figuring out how to treat cancer," Robertson said. "Where today’s cancer drug ‘cocktails’ sometimes poison nonspecifically, I think tomorrow’s treatments will target several specific proteins."

"This is where I see us going, long term," he said. "The patient will come into the clinic with metastatic melanoma and we’ll take a blood sample to profile what the ‘bad genes’ are for that particular person. Then we’ll be able to choose from an arsenal of drugs to give them a personalized treatment based on their own cancer. We’ll see better efficacy and lower toxicity."

"It’s my belief," Robertson said, "that our new drug will be in that arsenal."

Provided by Pennsylvania State University (news : web)

Filter


Move the slider to adjust rank threshold, so that you can hide some of the comments.


Display comments: newest first

deatopmg
Sep 30, 2009

Rank: not rated yet
Great work, but it is unlikely that a drug like this will ever get to market because it will cut a chunk out of the Industry's bottom line.
Rank 5 /5 (5 votes)
Relevant PhysicsForums posts
  • Is Everyday Technology Killing Us?
    createdFeb 08, 2012
  • Exercise and weight loss
    createdFeb 08, 2012
  • Why do we have head aches? Our brains can't feel anything.
    createdFeb 07, 2012
  • "The end of diseases" by David Agus, interview from Daily Show with Jon Stewart
    createdFeb 04, 2012
  • Oncolytic adenovirus
    createdFeb 04, 2012
  • Nutrition label stuffs and diets
    createdFeb 02, 2012
  • More from Physics Forums - Medical Sciences

More news stories

Researchers make breakthrough in stem cell research

(Medical Xpress) -- University of Queensland scientists have developed a world-first method for producing adult stem cells that will substantially impact patients who have a range of serious diseases.

Medicine & Health / Research

created 50 minutes ago | popularity 5 / 5 (2) | comments 0 | with audio podcast

Georgia Tech develops software for the rapid analysis of foodborne pathogens

2011 brought two of the deadliest bacterial outbreaks the world has seen during the last 25 years. The two epidemics accounted for more than 4,200 cases of infectious disease and 80 deaths. Software developed at Georgia Tech ...

Medicine & Health / Diseases

created 42 minutes ago | popularity not rated yet | comments 0

Can Viagra treat childhood lymphatic disorder?

(Medical Xpress) -- A surprising potential therapy for severe, hard-to-treat malformations of the lymphatic system is now being studied at the Stanford School of Medicine and Lucile Packard Children’s Hospital: researchers ...

Medicine & Health / Diseases

created 17 minutes ago | popularity not rated yet | comments 0 | with audio podcast

Don't ignore kids' snores

(Medical Xpress) -- Your ears aren’t playing tricks on you – that is the sound of snoring you hear from the bedroom of your preschooler. Snoring is common in children, but in some cases it can be a symptom of a ...

Medicine & Health / Diseases

created 7 minutes ago | popularity not rated yet | comments 0

WHO calls for stepped-up fight against leprosy

The World Health Organization called Monday for greater efforts to fight leprosy, warning the disfiguring disease was defying efforts to wipe it out across many countries in the Asia-Pacific region.

Medicine & Health / Diseases

created 13 minutes ago | popularity not rated yet | comments 0


New molecule has potential to help treat genetic diseases and HIV

(PhysOrg.com) -- Chemists at The University of Texas at Austin have created a molecule that's so good at tangling itself inside the double helix of a DNA sequence that it can stay there for up to 16 days before ...

With climate change, today's '100-year floods' may happen every three to 20 years: research

Last August, Hurricane Irene spun through the Caribbean and parts of the eastern United States, leaving widespread wreckage in its wake. The Category 3 storm whipped up water levels, generating storm surges ...

Researchers make better heat sensor based on butterfly wings

(PhysOrg.com) -- Scientists have long known that butterfly wings produce their iridescent colors by bouncing light around and between tiny ridges in structures made of chitin. More recently they’ve discovered ...

Social psychologist: Lust makes you smarter and evidence that seven deadly sins are good for you

(Medical Xpress) -- Good news for lovers on Valentine’s Day - the seven deadly sins, including Lust, are good for you. University of Melbourne social psychologist Dr Simon Laham uses modern research to make a compelling ...

The joy of cheques

An electronic cheque which eliminates the need for costly processing by banks but preserves the simplicity and ease of a traditional cheque book has been designed by a team of academics in the UK.

Research shows promise in converting camelina oil into jet fuel

(PhysOrg.com) -- Researchers at Montana State University-Northern have developed a process to convert camelina oil to jet fuel and other high-value chemicals. MSU has applied for a U.S. patent and research is ongoing.