Rodents and zebrafish against cancer

With the help of animal models, scientists have extended the lives of pancreatic cancer patients and used FDA-approved arthritis drugs to shrink skin cancer tumors.

Updated 25 March to include new FDA-approved skin cancer drug.

Genetically engineered mice and zebrafish enabled new research towards treatments for pancreatic and skin cancers, respectively.

1. Melanoma is the most deadly skin cancer, killing 8,700 Americans a year, and new research now suggests that an FDA-approved drug for rheumatoid arthritis could fight it.

Zebrafish can develop a form of the disease genetically similar to human skin cancer tumors.

From studying 3,000 of these genetically modified fish, a team led by Leonard Zon from the Children's Hospital Boston, discovered that it’s the excessive activity of certain genes – rather than the mutations to them – that drive melanoma.

They found that the gene SETDB1 plays a role in 70% of malignant melanomas.

In another study led by Zon, the team examined effects of various chemical compounds on pigments in zebrafish (and frogs too).

That led them to leflunomide – a generic drug commonly used to treat rheumatoid arthritis – which they found inhibits the growth of melanomas in tests with mice and human cells.

If further trials prove successful – both for leflunomide alone and in combination with Roche and Plexxikon's promising new melanoma drug PLX4032 currently in late stage trials – patients could have access to new treatments in 3 to 5 years.

Compared with each drug alone, the combo led to a marked decrease in melanoma, and even with low doses the tumors went away completely in 40% of the mice.

Both studies were published yesterday in Nature. Via USA Today and Reuters.

Update: On Friday, 25 March, the FDA approved Bristol-Myers Squibb's Yervoy (ipilimumab) to treat patients with late-stage (metastatic) melanoma.

2. Pancreatic cancer typically kills patients within a few months, but a new study shows how a treatment that fires up certain immune cells extended the lives of patients by more than 30%.

Unfortunately, that's only an extra 2 months, but that’s not bad if you consider how only 5% of patients with the most common form, pancreatic ductal adenocarcinoma (PDA), are alive 5 years after diagnosis.

One of pancreatic cancer's dirty tricks involves co-opting white blood cells. Instead of attacking, these turncoats infiltrate the cancer and "essentially wall it off from the antitumor effects of the immune system," says study author Robert Vonderheide of the University of Pennsylvania.

  1. First, they dosed PDA patients with a standard chemotherapy drug and an antibody that turns on CD40 – a protein carried by several kinds of our defensive cells.
  2. The pancreatic tumors either stabilized or shrank – and the patients survived 7.4 months.
  3. But to suss out the details, the team turned to mice genetically engineered to develop PDA.
  4. The chemotherapy drug and a rodent version of the CD40-activating antibody reduced tumors in about a third of them.

Turns out, the tumor-attackers were macrophages, a defensive cell who munch on bacterial invaders. Macrophages were able to squirm through the white blood cell blockade and start killing the tumor cells.

Now they want to figure out if other combos of treatments boost the activator's killing power, such as pairing it with a vaccine that incites immune cells to attack the tumor.

The study was published in Science earlier today. Via ScienceNOW.

Images: Wiki

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