Loading...

Weather Alerts 7 View »

Fruit Flies For Cancer: Medicine's Next Big Thing?

Fruit Flies For Cancer: Medicine's Next Big Thing?

CREATED Jun 24, 2013

DALLAS, Texas (Ivanhoe Newswire) - Rhabdomyosarcoma, or rhabdo for short, is a childhood cancer that often turns deadly. It only affects a couple hundred kids in the U.S. each year, but a diagnosis can be devastating. Now, doctors are close to a treatment and they have fruit flies to thank for it.

Sydney Mayrell loves crafts and cupcakes, but what she loves most is to play with her mommy.

Sydney and her mother have grown even closer since Sydney's diagnosis of cancer three years ago.

"I felt a lump in her left thigh," Erin Mayrell, Sydney's mother, told Ivanhoe.

That lump was rhabdo, an aggressive cancer that spreads through tissues in the body. For Sydney it meant 54 weeks of chemo, four weeks of radiation, and surgery.

"It can be a devastating disease. You're faced with no choice but giving them the most aggressive kind of therapy you can give," Rene L. Galindo, MD, PhD, Assistant Professor of Pathology, Molecular Biology, and Pediatrics at UT Southwestern Medical Center, Dallas, told Ivanhoe.

Dr. Rene Galindo hopes his research in fruit flies will change that. In the lab, he was able to show that silencing a specific gene in the flies prevented healthy cells from becoming cancerous and turned cancerous rhabdo cells back to normal! He was able to replicate the same results in human tumor cells.

"The cancer would stop being a tumor and it would become normal skeletal muscle," Dr. Galindo said.

The next step is a clinical trial in humans. If it works, it could essentially be a cure. That has Sydney and her mom excited. She's in remission now, but this good news is icing on the cake.

Dr. Galindo said this method of gene silencing would offer a much less toxic and less harsh treatment for children. Rhabdo tumors usually occur in children under six years old.

RESEARCH SUMMARY

BACKGROUND: Rhabdomyosarcoma is a type of sarcoma, which is cancer of soft tissue, connective tissue, or bone.  It is the most common type of soft tissue sarcoma in children and can begin in many places in the body. However, it usually begins in muscles that are attached to bones and that help the body move.  Soft tissues of the body connect, support, and surround other organs and body parts.  Soft tissues include: nerves, fat, blood vessels, lymph vessels, fat, muscles, tendons, and synovial tissues (tissues around joints). There are three main types of rhabdomyosarcoma: embryonal, alveolar, and anaplastic.  Embryonal, which is the most common type, occurs most often in the head and neck area or in the urinary or genital organs.  Alveolar occurs in the arms or legs, chest, genital organs, abdomen, or anal area, and it usually occurs in the teen years. Anaplastic is a rare type that occurs in children.  (Source:www.cancer.gov)

RISK FACTORS:  Risk factors include the following inherited diseases: Noonan syndrome, Costello syndrome, Beckwith-Wiedemann syndrome, pleuropulmonary blastoma, neurofibromatosis type 1, and Li-Fraumeni syndrome.  Children who had a high birth weight or were bigger than expected at birth have an increased risk of embryonal rhabdomyosarcoma.  (Source: www.cancer.gov)

SYMPTOMS:  Childhood rhabdomyosarcoma can cause lumps and other symptoms, but the symptoms depend on where the cancer forms.  Symptoms can include bulging of the eye, blood in the urine, bleeding in the nose, throat, vagina, or rectum, headache, trouble urinating or having bowel movements, and swelling that keeps getting bigger and more painful. (Source:www.cancer.gov)

NEW TECHNOLOGY: The traditional treatments of chemotherapy, surgery, and radiation for rhabdomyosarcoma can result in disfigurements and disabilities.  The newest breakthrough in improving treatments comes from UT Southwestern Medical Center.  Researchers identified the role for a gene, called TANC1, to convert normal muscle cells in fruit flies into cells that behave as aggressive Rhabdo-type cells. By silencing the gene, researchers convert healthy cells to a non-cancerous state. "This suggests a completely different way of caring for Rhabdo – by targeting this particular gene. If we take down TANC1 activity, it essentially rescues these cells from their neoplastic state and gets them to complete their developmental process," Dr. Rene Galindo was quoted as saying.  In a previous fruit fly study, the Galindo lab learned that over-expression of a gene, called PAX-FOXO1, caused muscle cells to improperly fuse.  The newer study revealed that PAX-FOXO1 is dependent on TANC1 in making muscle cells go awry. (Source: http://www.utsouthwestern.edu/newsroom/center-times/year-2012/may/galindo-research-rhabado.html)

INTERVIEW

Rene L. Galindo, MD, PhD, Assistant Professor of Pathology, Molecular Biology, and Pediatrics at UT Southwestern Medical Center, talks about a possible cure for Rhabdomyosarcoma.

What is Rhabdomyosarcoma?

Dr. Galindo: We call it Rhabdo for short. It is a malignant cancer that looks somewhat like skeletal muscle. For the record, Rhabdomyo is actually Latin for skeletal muscle. So, that's why it's called Rhabdomyosarcoma.

What happens when you have this type of cancer?

Dr. Galindo: It can be a devastating disease in the sense that it's not the type of tumor that is contained within an organ. For example, in colon cancer you can take out the representative segment of colon and hopefully cure the patient. These are tumors that can be anywhere in the body and they're not confined to any boundaries; so they just grow and spread and spread out.

Is it like lymphoma?

Dr. Galindo: Yes, in a way. The way that you would like to treat these tumors is to be able to go in surgically and just take the entire tumor out and know that you have taken out the entire tumor. Unfortunately, way too often the tumor has gotten too big to do that. So, to take out the entire tumor you would have to take out too much of the surrounding body tissue and you don't want to do that to kids who have growing tissues.

So do these kids have just one tumor or multiple tumors?

Dr. Galindo: It's always starts out as one tumor. If you catch it too late it can metastasize and once you have a metastasis you can't just take out just the one tumor. You are at that point battling all of these different tumors that have spread throughout the body. So, that's why these kids have to go through devastating chemotherapy and radiation, which for growing kids you just don't want to give them something that's going to hurt anything other than the tumor. So, you're faced with no choice but to give them the most aggressive kind of therapy you can give and that will put them at risk for long-term complications. As well as the damage that chemotherapy, radiotherapy, and radiation therapy can do.

When you talk about chemo, most people think it is for 30 days or four weeks. How long do these kids have to be on it for?

Dr. Galindo: The intervals could be months to a year, depending on how aggressive the therapy needs to be. Unfortunately, if you look at a kid that has had a lot of chemotherapy you can tell what the body has been subjected to it. They don't grow quite as well. They will look like a child who should be 10, but looks like they are six or seven. They will have siblings that don't have cancer and haven't been treated that are two or three years younger, but those siblings will actually be bigger, stronger, and taller than the kids who have gotten chemotherapy. So, you can see how when you give kids these powerful drugs it has an effect on how their body grows and how their body matures. The last thing that you want to have for kids are things that leave disfiguration's or leave them looking different. We all remember what it was like to be a kid and to feel like you look different. So, to treat this tumor in kids in a way that gets the tumor, but also does as little damage to the surrounding normal tissue, is a primary goal for me and everyone else.

So, how are you doing that?

Dr. Galindo: We came up with a way of doing it that was, at time, a little unique and fortunately I had good mentorship that encouraged me to go ahead and try to study rhabdo in a different way. The most aggressive form of childhood Rhabdomyosarcoma has an equivalent version of the gene that is in the DNA of species throughout evolution; so to do it in mice is obviously an experimental approach. We, however, turned altogether to a completely different model and looked at fruit flies as a new system to make insights about this gene. Drosophila melanogaster, the species name for this type of fruit fly has been used as an experimental model system for centuries. The applicability of the model system has been recognized with multiple Nobel prizes.

The main thing is if you look at the gene that is damaged in human Rhabdomyosarcoma, there is a version of that gene in the fruit flies that is on the DNA level and on the protein level essentially the same. What people hadn't been able to do in the past for a number of different reasons was to manipulate that gene genetically in the fruit flies, so the fruit flies would then suffer from effects from that damaged gene similarly to what happens to humans cells when they have that damaged genes. So, we manipulated the fruit fly's DNA and changed that gene to represent a completely identical fashion to the damaged human gene, which generated a whole new genetically modified type of fruit fly that suffers from symptoms that are similar to what kids have. Then what we were able to do from that point was to systematically manipulate other genes in the genome of the fruit fly and find other genes that cooperate with the original diseased genes to cause the nasty behaviors of the human Rhabdomyosarcoma cells. We were thinking that, since no diseased gene ever functions alone, there must be other genes in human cells that work in concert to cause the full type of symptoms in rhabod.

Have you been able to cure the fruit fly?

Dr. Galindo: We can actually mutate additional genes, like I mentioned, and you find that these particular genetically engineered fruit flies are completely resistant to the disease process. Thus, we hypothesized that if we made similar changes in these cooperative genes in human cells the Rhabdomyosarcoma cells would stop being malignant and become normal skeletal muscle cells. That's what we have been able to do. By starting with an experimental model that is easier to manipulate and to study, we were able to identify new important biological entities and processes that we can now hope to exploit clinically.

Will you be able to stop it? Will you be able to cure it? Will you be able to just stop the symptoms?

Dr. Galindo: A good example would be one particular gene right now that we think is really important. We think we have a drug that specifically puts the behavior of this gene back in check. We've been putting this drug on human Rhabdomyosarcoma cells and sure enough it seems to be correcting the behavior of that gene and converts the cancer cells to otherwise normal skeletal muscle cells. So, the next thing that we obviously want to do is to find a way to actually bring that into a clinical trial, which we are optimistic. If it ends up being effective with rhabdo kids, we are very hopeful that we can take these tumors and convert them from a state of being aggressive and malignant to a state of being normal skeletal muscle - so that the cancer goes away.

So the cancer would just disappear?

Dr. Galindo: The cancer would stop being a tumor and it would become normal skeletal muscle that would have no negative features in the human body.

Could this work in all types of cancer?

Dr. Galindo: That would be something that we would obviously look into and test. There are other tumors that are somewhat related to Rhabdomyosarcoma. So, we would like to extend our studies out from that and see if other tumors would respond.

Do kids only get this type of cancer?

Dr. Galindo: Yes, though there are exceptions. There is a type of Rhabdomyosarcoma that adults can get, but the one with this particular original diseased gene that we focused on is relatively unique for kids and young adults. It's a soft tissue tumor, not a bone tumor or a lung tumor. Well it turns out that there's a whole family of soft tissue tumors, called sarcomas, which only kids get. So, we think that there is something different about growing ­­­childhood cells that make them uniquely susceptible to these particular types of malignancy. We think that there's going to be overlap between the most common four or five childhood sarcomas.

FOR MORE INFORMATION, PLEASE CONTACT:

Rene L. Galindo, MD, PhD
Assistant Professor of Pathology, Molecular Biology, and Pediatrics
UT Southwestern Medical Center
Rene.Galindo@UTSouthwestern.edu
(214) 648-4093