'Suicide' Gene Kills Brain Cancer - NewsChannel5.com | Nashville News, Weather & Sports

'Suicide' Gene Kills Brain Cancer

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SAN DIEGO, Calif. (Ivanhoe Newswire) – Twenty three thousand people will be told they have brain cancer this year and 13,000 will die. Now, a gene with a death wish is helping destroy life-threatening tumors.

Every day, everyone in the Kass family heads outdoors to skate and scoot. Always watching nearby is mom, Marni Grass. It was right after her little girl Sloan was born that Marni started feeling strange.

"I had really bad headaches," Marni told Ivanhoe. "I didn't know what it was."

She thought she was suffering from postpartum depression, but what she had was a brain tumor.

"Marni looked at me and said ‘See I'm not crazy!'" Paul Kass, Marni's husband said.

She had surgery to remove it, then chemo and radiation to kill what was left, but it wasn't enough. She was given four months to live and now three years later she's still fighting.

"They actually have tentacles that spread into the brain, and that's why we have a hard time getting it all out," Santosh Kesari, M.D., Ph.D., a neuro-oncologist at UC San Diego Moores Cancer Center, explained.

Marni is one of the first patients in the country to have a virus injected into her brain to kill the cancer.

"When we inject, the virus infects the next cell and spreads to the next cancer cell," Dr. Kesari said.

Doctor Kesari said a virus called Toca 511 carries a suicide gene to cancer cells. It keeps replicating as it finds more cancer cells. After four weeks, patients are given a drug that's activated by the suicide gene.

"That gene converts it to a chemotherapy drug," Dr. Kesari said.

It delivers a toxic dose to the cancer cells without harming healthy cells in the brain. Marni is hoping this is the procedure that wipes out her tumor for good and allows her to focus on her family.

Doctor Kesari believes using suicide genes could someday be the norm for treating all different types of cancer. That could mean there would no longer be the need for open surgeries. Instead, just a biopsy to deliver cancer fighting drugs.

RESEARCH SUMMARY

BACKGROUND: Glioblastoma (GBM) belongs to a family of brain tumors called "astrocytomas." These are tumors which arise from astrocytes – star-shaped cells of the brain which play a role in supporting normal brain tissue. There are four stages of astrocytoma and GBM is the fourth; it is also the most aggressive type of nervous system tumor. (SOURCE: www.abta.org, www.ncbi.nlm.nih.gov/pubmedhealth, www.webmd.com)

SYMPTOMS: General symptoms of GBM are essentially the same as for other brain tumors, they include, headache, weakness, seizures, clumsiness; and having difficulty walking.
Specific symptoms will depend on the size and location of the GBM. The symptoms of brain cancer are numerous and not specific to brain tumors, meaning they can be caused by many other illnesses as well. The only way to know for sure what is causing the symptoms is to undergo diagnostic testing (SOURCE: cedars-sinai.edu, WebMD)

TREATMENT:
The standard method of treating GBM has been essentially unchanged for many decades—surgical resection of as much of the tumor as is safe, followed by radiation therapy and chemotherapy (usually designed to damage DNA or to otherwise inhibit DNA replication) (SOURCE: www.ncbi.nlm.nih.gov/pubmedhealth)

KILLING BRAIN CANCER: Cancer cells are able to replicate, but there's a trade-off: They cannot ward off infection as effectively as healthy cells. So scientists have been looking for ways to create viruses that are too weak to damage healthy cells yet strong enough to invade and destroy tumor cells.

UC San Diego Moores Cancer Center researchers and surgeons are among the first in the nation to treat patients with recurrent brain cancer by directly injecting an investigational viral vector into their tumor.

The trial is investigating the use of Toca 511 for injection in combination with Toca FC, extended-release tablets. Toca 511 is a retroviral replicating vector that is designed to deliver a cytosine deaminase (CD) gene selectively to cancer cells. After allowing time for the administered Toca 511 to spread through the cancerous tumor those cancer cells expressing the CD gene can convert flucytosine into the anti-cancer drug 5-fluorouracil. In this study, patients receive cycles of oral Toca FC monthly for up to six months.

INTERVIEW

Dr. Santosh Kesari, a Neuro-oncologist, Associate Professor of Neurosciences, and Director of Neuro-Oncology at UC San Diego Moores Cancer Center talks about a virus and gene that kills itself to save brain cancer patients.

What are glioblastomas?

Dr. Kesari: Glioblastoma is the most common type of malignant brain tumor that we deal with. It is a tumor that arises in the brain and is actually quite aggressive and tends to be very resistant to our standard treatments.

What can glioblastoma do to a patient?

Dr. Kesari: Since it arises in the brain, patients have problems with many functions, including motor skills, memory changes, cognitive function, ability to speak, or vision loss, that is how they present with these types of tumors. One of the difficult aspects of these types of tumors is, they look like a lump on imaging, but they actually have tentacles that spread into the brain, and that is why we have a hard time getting it all out surgically or treating all of it with radiation and chemotherapy.

If you do not get it all out, does it just grow back?

Dr. Kesari: Yes. That is one of the big problems that we have with this disease is the fact that they do have tentacles into normal brain where we cannot access through surgery and even radiation. We do not want to radiate the whole brain so we will have to rely on either chemotherapy getting throughout the whole brain or other methods to really try to make a big impact on this disease.

What is the traditional treatment?

Dr. Kesari: Traditionally we do optimal surgery where we try to get out as much as possible and as safely as possible. I think that this improve outcomes in our patients. We follow that with radiation. We radiate what the tumor bed and a margin of normal brain to try to get those infiltrating cells. We use chemotherapy along with radiation to further improve killing tumor. The reality is, even with this standard treatment, these tumors uniformly come back. For most patients, it comes back within a year or two after treatment. We still need to improve on the ability to detect tumor cells that hide in the brain and cannot be seen on an regular MRI. That is really one of the big problems that we deal with and why we are probably not as successful as we should be because we are not treating these cells that are invading the brain.

How can you get these cells?

Dr. Kesari: One way is to get better drugs that actually go into the normal brain and find these invading cells. Most of the drugs we use tend to go into the tumor, but may not get these invading cells. There are other methods to try to get drugs across the blood-brain barrier that people have been working on, and then there are more novel approaches such as using replicating viruses to kill brain tumors. I did this type of work for my Ph.D. thesis using herpes simplex virus vectors that replicate in and kill tumor cells, but not the normal brain.

But you are not using the herpes virus for this, correct?

Dr. Kesari: At this time, we are not using herpes viruses. We are working on a Tocagen company sponsored clinical trial involving a retrovirus that replicates in tumor cells and carries a suicide gene called cytosine deaminase, which converts a benign antifungal drug called 5-FC into 5-FU, a toxic chemotherapy drug. You optimize delivering the drug to tumor cells and then, reduce the side effects to the normal brain.

Does the virus replicate?

Dr. Kesari: The good thing about this virus compared to the previous generation of viruses, is that it actually replicates and this was one of the hurdles that the company had to overcome in terms of approval by the FDA. This is because in the past, we have generally used viruses that are not able to replicate very well. They were used in human clinical trials and they were not as effective as we wanted them to be. So the approach of using a replicating virus is quite novel.

Will it work if more cells pop up?

Dr. Kesari: In theory, that is right. It will, when we inject one tumor site, infect those cells around it and then make more of itself and then spread further. After the surgery, we wait about 4 weeks to allow this replication process to happen. Then we give the drug at that point and presumably the virus has spread throughout the tumor and maybe even into those cells that are invading the normal brain.

Is there no other damage?

Dr. Kesari: In theory, there is no other damage.

Now, in your clinical trial, what have you seen?

Dr. Kesari: It is still in early stage so hard to say at this time.

Can you talk about Marnie?

Dr. Kesari: Marnie is a patient of mine. She has an unusual brain tumor actually. We thought it was initially a slow growing tumor several years ago and after our standard biopsy, radiation and chemotherapy, it actually became a more malignant tumor. She has had multiple rounds of different treatments. She has responded well to them and more recently, it started growing slowly over the last 6 months or so.

How have you seen her change through this whole process?

Dr. Kesari: Brain tumors affect your soul, because it involves your brain and your mind. What we tend to see in our patients is, depending on where the tumor is located, a progressive decline in functions. As you will see in Marnie's case, there is weakness developing on one side, so it is becoming difficult for her to ambulate and move around.

After the tumor is gone, can she regain that?

Dr. Kesari: Sometimes, yes. If the deficits are due to swelling and the tumor has not actually involved the motor fibers yet, it's possible. If we can get rid of the tumor by surgery, by radiation or by new treatments and we shrink it, then those symptoms can improve over time.

Is Marnie part of the clinical trial with the virus?

Dr. Kesari: Yes, Marnie had the virus injection because she has failed all the other standard treatments already. We are really left with no other options at this point. That is why she was very interested in this clinical trial and that is why we worked hard to get her on this clinical trial.

Is this the last hope for sufferers?

Dr. Kesari: No, there are many clinical trials available and particularly this clinical trial, there is a lot of interest from many of my patients to participate because of the novelty of it, the fact that most of the drugs that we tried do not have very good effects. The fact that there is encouraging data, even from the ongoing clinical trial of patients, is also a plus.

What makes this different from the herpes virus?

Dr. Kesari: I think one unique thing about it is that this is a replicating virus. The other novelty is the fact that they are carrying a suicide gene. In the future, they could add more genes to try and combat the tumor in multiple ways.

Will this ever be a first line of defense before surgery?

Dr. Kesari: Usually we do these studies to prove that there is activity in patients who failed our standard treatments, and then if we see activity we move it to the first line with radiation and chemotherapy. If you had a really effective treatment, you could one day, instead of doing big surgeries, just do a biopsy, make a diagnosis and then inject the virus or other drugs and then be able to shrink the tumor without having to do big surgeries. That would be the goal in the future as we get more effective treatments.

FOR MORE INFORMATION, PLEASE CONTACT:

Santosh Kesari, MD, PhD
UC San Diego Moores Cancer Center
(858) 822- 6346
skesari@ucsd.edu

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