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Shocking Away Melanoma

Shocking Away Melanoma

CREATED Dec 10, 2013

SAN FRANCISCO, Calif. (Ivanhoe Newswire) - Each year, more than 76,000 Americans are diagnosed with melanoma, and 9,000 die. Once its spread, this type of cancer is extremely difficult to treat. Now, researchers say a new therapy is helping them shock away some of the most stubborn tumors.

With 20 acres of grapes to grow, animals to feed, and grass to cut, Martin Bajuk is a busy man.

"There are always things to do," Martin told Ivanhoe.

However, a recent diagnosis of melanoma threatened to slow down this active 77-year-old.

"I noticed sort of like a wart" Martin explained.

He had three surgeries, but the cancer spread and Martin was running out of options.

"It's a frustrating cancer to treat, and it's also very resistant," Adil Daud, MD, Medical Oncologist, University of California, San Francisco, told Ivanhoe.

Dr. Daud is studying electroporation for advanced melanoma.   He injects a gene–called IL12 into the tumor and uses this device to deliver electricity. The charge opens pores in the tumor so it can absorb the IL12. Then, the body's immune system sends special cells to destroy the cancer.

"Then, once the immune system has done that, there's what's known as memory cells, and so those memory cells circulate around and if they see other melanoma, they will get rid of that too," Dr. Daud explained.

In a trial, eight of nine patients saw all or most of their tumors shrink. None reported side effects. One downside—the treatment is painful. Just ask Martin.

"It's over 1200 volts of electricity. That is just unbearable," Martin said.

However, the pain lasts for just a second and with his cancer in check, Martin can focus on what he loves most, working in the outdoors.

The procedure is given three times over eight days. Each shock lasts only a few milliseconds. Researchers say this therapy would likely be combined with others to see maximum benefits. Five other centers around the country are involved in the electroporation study.

RESEARCH SUMMARY

BACKGROUND: Melanoma is the most dangerous form of skin cancer. It happens when skin cells are damaged. Typically, this happens when a person subjects themselves to ultraviolet radiation from the sun or tanning beds. This disease causes skin cells to multiply and form noncancerous (malignant) tumors. Usually, melanomas develop from moles or are mistaken for moles. They have a brown or black color to them, but they may also be blue, purple, skin-colored, pink, red, or white. Melanoma kills 8,790 people a year in the U.S. and it is one of the most under-estimated cancers. (Source: http://www.skincancer.org/skin-cancer-information/melanoma)

TYPES: There are four basic types of melanomas that affect the skin. Three of them are less invasive and the other is invasive from the start. Superficial spreading melanoma is the most common type. This begins on the surface of the skin, then will infiltrate deeper. Lentigo melanoma is mostly found in the elderly and is very similar to superficial spreading melanoma. When it first develops, it is a tan, brown, or black discoloration and usually lays flat on the skin. Acral lentiginous melanoma also spreads like superficial melanoma, but it surfaces under the nails, palms, or soles of the feet. The last type is Nodular melanoma and this is the most invasive form of the disease. It is very dangerous, and usually forms as a bump that is a blue, black, gray, white, red, or tan color. (Source: http://www.skincancer.org/skin-cancer-information/melanoma/types-of-melanoma)

NEW TREATMENT: A new technology is offering hope to patients suffering from metastatic melanoma. It's a combination of genetic engineering and electricity being tested at the University of California, San Francisco. Researchers inject DNA plasma into the area of the melanoma. It is genetically engineered to produce a protein called interluken-12.  Then, they deliver a volt of current into the same area, using a device manufactured by San Diego-based OncoSec. This process is called electroporation.  The electric shock causes the pores in the cancer cells' membrane to open just long enough to allow the plasma to enter.  Once inside, the cells begin producing interluken proteins, which are treated as an alarm signal by the body's immune system, which then attacks the cancer cells. "IL-12 is a very powerful immune-stimulating protein. There was excitement for IL-12 in the 1980s and 1990s, but systemic toxicity prevented further development of it. Since that time, investigators have been trying to deliver IL-12 in creative ways, and this is one example of such an approach," Shailender Bhatia, MD, of the Seattle Cancer Care Alliance in Seattle, was quoted as saying. (Source:http://www.ascopost.com/ViewNews.aspx?nid=7369 andhttp://clinicaltrials.gov/show/NCT00006035

INTERVIEW

Adil I. Daud, MD, Medical Oncologist, University of California, San Francisco, talks about a new treatment that is "shocking" away melanoma.

Is the advanced stage melanoma hard to treat?

Dr. Daud: It is very hard to treat. If you look at the statistics from a few years ago, only about 10 to 15 percent of patients with advanced stage melanoma would be alive at 5 years. Now, I think the numbers are better.

Why is it so hard to treat?

Dr. Daud: I think part of the problem is that it isn't sensitive to chemotherapy. If you look at other cancers like breast cancer or colon cancer, where we've made big advances, I think those have been cancers that are very responsive to chemotherapy. So, you can eradicate a good portion of the cancer at the time of surgery, or after surgery, and so you can keep a lot of those patients from coming back and developing advanced cancer. In regards to melanoma, the problem has been that we've tried again and again with different types of chemotherapy and it's just not a chemo sensitive tumor. The response to chemotherapy has been in the ten percent range, where ninety percent of patients don't have a response. When you're trying to cure a disease with a ten percent response rate, chances are you're missing a lot of cells. Those cells can start dividing and cause problems.

Targeted therapy has been a big advance, but the problem with targeted therapy has been that ultimately a lot of people will develop resistance to targeted therapy. It starts off working great, but six months or nine months later people will develop resistance to it and so their tumors will start growing again. Another big advance in our field has been in immunotherapy, harnessing the body's immune system to fight these tumors. So, that's been super successful I would say. I think there are still some challenges in immunotherapy. There are autoimmune side effects that immunotherapy can unleash and so you've got to control those autoimmune side-effects so that you know they don't affect the person's quality of life a whole lot. Another problem with immunotherapy is that even today; only a certain number of patients will respond to immunotherapy, for the other 40 or 60 percent of folks, we don't know why exactly their immune system is not recognizing their melanoma.

Is it a frustrating cancer to treat?

Dr. Daud: It is a frustrating cancer to treat and it's also very resistant. Often times the cancer will evolve. People say that they are smart tumors and there are dumb tumors and melanoma is definitely one of the smart tumors that finds ways around a lot of treatments.

How are electro impulses changing the game?

Dr. Daud: The way electro impulses are changing the game is at the point where you have melanoma that's spread, but it's still accessible to the surface. For instance, if it's under the surface of the skin, in lymph nodes, or in a place where you can reach, like your chest wall, thigh we can actually deliver genes directly in to the tumor. You can pick whatever gene you want, but the one we focused on is the gene called interleukin 12, which is a molecule that the immune system uses to signal danger. The melanoma tumor now has this giant flashing light on it that makes it visible to the immune system. So, it makes your immune system see that that's all is not well, you know, stream in to the tumor and get rid of it. Then, once the immune system has done that, there are memory cells and so those memory cells circulate around, and if they see other melanoma they'll get rid of that too.

Are there any downsides to this because isn't it all noninvasive?

Dr. Daud: The biggest downside we've found so far is that the electric shock itself is kind of unpleasant. It's a little bit like sticking your finger in an electric socket. You know how you get that jolt or you touch like a light terminal, a battery, or something like that, that's how it feels like. The electric jolt will only last for a few milliseconds. We have done this in a lot of patients and what almost everybody says is that once the impulse is done you're back to normal. There's no nausea, no vomiting, no hair loss, and very few side-affects following it. However, while you're having it done it's kind of unpleasant and we use medicines to reduce all that discomfort and pain and also use some local anesthetic to numb the needle. Because the probe has six needles in it and so that goes into the lesion; so, you kind of feel like something is sticking into that lesion and we use a local anesthetic so you won't feel the pain of the needles going in. However, you do feel that electric jolt. I think that's the major disadvantage.

Does all melanoma start on top of the skin?

Dr. Daud: Not all, but the majority starts on top of the skin. There are a couple of different types of melanomas that don't start on the top of the skin. There's one kind of melanoma that starts in the pigment layer of your eye, behind your retina or in your iris. So, that's known as ocular melanoma.. Then, there's a second kind of melanoma that starts in your mucus membranes and it's found in your in the nasal cavity, in the nasal mucosa, in the rectum, and vagina. So, that's a kind of melanoma that we don't think is related to sun exposure. It's related to something else, we don't know exactly what it's related to.

Would this work on some of those types of melanoma as well?

Dr. Daud: I think it could, but we haven't tested it on mucosa melanoma or on ocular melanoma partly because they're unusual and also because you'd have to do it in in that location and so it's just a matter of finding somebody who is a suitable candidate and if they are interested in doing it.

So, are you involved in a second trial with this?

Dr. Daud:  Yes.

Tell me a little bit about that and it says that 95 percent of treated lesions showed some response?

Dr. Daud: Yes, that's right. So, that has to do with the local efficacy of the treatment. Let's say if you have a lesion here or a lesion here you do the electro operation on the lesion, the vast majority of lesions will regress and either shrink down or just totally disappear. I think that's impressive, but I think that's not as impressive as the fact that you'll get distant lesions to respond. The reason I think that is because when you have distant lesions responding that's telling you that your immune system is woken up and is on the case. So, if you your cancer divides and decides to go to some new place, you'll still have some activity against the cancer. That is why I feel this is so exciting, the fact that you're having this kind of vaccine effect almost.

Do you see this as a cure?

Dr. Daud: I think so. I mean it's a part of a cure. I don't think in the current form it's a cure partly because it only been through Phase I and Phase II testing; so I think there is a long ways to go before we can say that it's that good.

Can you tell me a little bit about Martin?

Dr. Daud: He is a gentleman who's a super active guy. He golfs. He's an outdoorsy person, very active, just a wonderful human being. He had melanoma on his leg, close to his ankle. He had that taken out, had a recurrence there, that was taken out also. Then, what was noticed is that he started having melanoma spots develop just above his ankle. We know from the history of melanoma that this type of melanoma, which is called in-transit disease, where you know the melanoma starts recurring outside of the area where the surgery was done is sometimes a precursor to wide spread disease. So, if you could stop it at that point that would be wonderful. That is what we're hoping to do for him.

If this treatment doesn't work for him, what are his best options?

Dr. Daud: The other options for him would be surgery, which he's had a couple of times, but you can have surgery more times. You could keep on taking more chunks of skin off. The other option would be systemic treatment like chemotherapy, immunotherapy, or targeted therapy. Then, the third option would be something known as limb profusion where chemo is infused in to your limb and it's a pretty extensive kind of surgery that lasts eight or nine hours. 

FOR MORE INFORMATION, PLEASE CONTACT:

Elizabeth Fernandez
UCSF Senior Public Information Representative
415-514-1592
Elizabeth.Fernandez@UCSF.edu