Researchers discover how UV rays cause melanoma


The_sun1

How can sunlight or UV exposure cause melanoma?

Researchers have now pinpointed how this works, and why some individuals are more at risk than others to develop the disease. This is a critical discovery for melanoma. As it is with potential treatment or cure, once you can pinpoint the right question the solution often naturally follows.

Arup Indra, an associate professor at Oregon State University’s Health & Science University College of Pharmacy says they’ve discovered how melanoma works, and has unlocked the mystery of why the disease strikes some, and not others.

“We believe this is a breakthrough in understanding exactly what leads to cancer formation in melanoma,” said Indra. “We’ve found that some of the mechanisms which ordinarily prevent cancer are being switched around and actually help promote it.

“In melanoma, the immune system is getting thrown into reverse,” he said. “Immune cells that previously were attracted to help deal with a problem are instead repulsed.”

This research shows melanoma is an immune-type of disease, since the physiological break-down happens way early in the process of UV damage and repair. Quite simply, those with melanoma have immune systems which failed to kill defective or damaged skin cells in specific areas before they became malignant.

The average human body has 60,000 melanocytes – so why might some cells develop melanoma and others don’t?

One curious detail not mentioned in Oregon State University’s research (online, anyway) is why melanoma doesn’t just happen system-wide. I mean – if it’s an immune-disorder, wouldn’t it effect all melanocytes? Why does melanoma occur just in patches, or one mole? Perhaps that question alone may help shed light on how the immune system works with melanoma, and maybe even other immune-type of diseases too. It would seem that only some cells are affected, and only some parts of your body can have immune system problems – that alone is an interesting phenomenon. Perhaps this means the systemic, throw-the-whole-paint-can-on-the-wall approach to medication for this and other conditions means medicine should not only be personalized, but pinpointed with extreme accuracy.

This might also explain why surgery and early detection have high success rates – because melanoma will begin in patches – not all over your body at once. For example, if you have a sunburn and develop a tiny melanoma lesion, the melanoma is not automatically everywhere you’ve burned. It’s not system-wide, even when metastatic. Most of your immune system still works properly. A good thing to be sure – but why is that? Why is it that some cells are affected and others aren’t? They don’t know the answers to those questions yet – but they do know how melanoma works on a cellular level now.

How melanoma works

In areas of patches not able to heal fast enough, cells which are not killed off by the immune system – in this case melanoma cells – can invade. To make matters worse, the damaged, mutated cells grow out of control, taking over otherwise healthy areas of skin before it has a chance to grow and replace normally.

Here’s the process step by step – which is important, since different treatments work with different phases of the disease:

  1. A person is exposed to UV rays, with or without burn
  2. Melanocyte cells are damaged in the process
  3. The immune system fails to kill damaged cells in one area of the body due to immune suppression
  4. The mutated cells, now with DNA damage, grow (since the immune system still won’t suppress them)
  5. Other skin cells are die normally (normal life cycle)
  6. The mutated melanoma cells grow in and take the place of where new healthy cells should be and result in a melanoma lesion (can be surgically removed if caught very early)
  7. The lesion spreads to near or distant tissue (metastasis – treated by chemo/immunotherapy meds, surgery, radiation)

This moves treatment close to prevention (or position #1 above) by testing people’s level of RXR (retinoid-X-receptors). This is a protein which aids in the proper operation of the immune system in the skin. With a test like this we’d know who’s at risk for developing melanoma, and who of us should start wearing a burka.

Kevin’s current treatment, Mekinist and Tafinlar pills, deals with step 6 above, by blocking the cellular pathway to stop the growth of melanoma tumors. What that means is it prevents a particular protein that helps cancer cells grow. Only about 50% of melanoma patients have the V600 E or K gene mutation, but mutated BRAF genes are often behind many different types of cancer – not just melanoma. Mutated, it causes cells to grow uncontrollably in various places.

While there’s research going on now to figure out how to prevent people’s bodies from eventually rejecting this treatment, your body still needs healthy BRAF genes to direct cell growth, which is probably why this type of treatment is only effective for several months.

Anti-PD-1, what Kevin will receive in a few weeks, has the potential to jump up to #3 in the chain of events. Anti-PD-1 (or MK3474) is designed to unmask the mutated cells so the body’s natural immune system (T-cells) can recognize the mutated cells for what they are, and kill them.

Yervoy, which Kevin must take before Anti-PD-1, does not work with the chain of events above, but merely takes the brakes off of his immune system. So the immune system basically goes as wild, and can proliferate as much as the cancer.

 

 

Clearly this exciting discovery opens research in many different areas, as researchers do the detective work needed to find the ultimate cause. Here are some links if you’re interested in learning more.

Oregon State University discovers how melanoma works.

Researchers at Oregon State University have identified a specific biochemical process that can cause normal and healthy skin cells to transform into cancerous melanoma cells, which should help predict melanoma vulnerability and could also lead to future therapies.

 

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s