Nav: Home

Gene therapy against brain cancer

May 13, 2016

Only a few days ago, the press (especially in English-speaking countries) enthusiastically announced the publication of a study that described in great detail the genetics of breast cancer, a discovery that according to many marks a breakthrough in the battle against this cancer. This kind of news confirms the impression that in the near future the war against cancer will be fought on the battlefields of genetics. Italy too, is working on this front. At SISSA, for example, where Antonello Mallamaci and his group have just published highly promising results on the application of gene therapy against glioblastomas, a family of brain tumours among the most common and aggressive. A diagnosis of glioblastoma is literally equal to a very imminent death sentence: "surgery is rarely curative, as these tumours insinuate themselves in healthy tissues, and also chemo- and radiotherapy have little effectiveness. In a short while, very aggressive recurrences develop and that marks the end" explains Antonello Mallamaci, SISSA professor who also collaborates with the Telethon Foundation. "Our approach is radically different: we introduce an additional copy of a given gene into the tumour cells so as to impair their reproductive capacity and lead them to suicide".

The idea for this study came to Mallamaci - who is not an oncologist - after years of close investigation of a particular gene called Emx2. One of the characteristics of this gene, explains the scientist, is to inhibit proliferation of astrocytes during embryonic growth. Glial cells, including astrocytes, are part of the nervous system, where they nourish and protect neurons and finely regulate their function.

"We know that during the early stages of development of the nervous system only neurons grow, whereas glial cells only start to proliferate when neuronal growth is practically complete", explains Carmen Falcone, SISSA research scientist and first author of the paper. "In our previous studies we discovered that Emx2 is expressed at very high levels during the neuronal generation phase, whereas its action declines dramatically when the glial cells start to grow. So the gene keeps astrocyte growth in check up to a certain point".

If it can block astrocytes, why not try and use it to block glioblastomas? "These tumours share many features with astroglia" comments Mallamaci, "hence the idea to use them to our advantage. With the contribution of IST in Genoa, which supplied us with cultures of various types of glioblastoma, we started doing some in vitro tests". And these tests went "beyond our rosiest expectations", explain Falcone and Mallamaci: "in nearly all of the samples, the tumour tissue literally collapsed in less than a week.".

At this point the study continued in two directions. The team first modelled in vitro the molecular mechanisms intervening between when the therapeutic gene is "switched on" and the final effect, finding that the gene attacks tumour metabolism at no less than six points, a result defined as "very robust" by the researchers.

A Trojan horse inside the tumour

After the in vitro studies, the group started its first in vivo experiments on mice, adopting all due precautions to prevent unacceptable suffering of the animals. "So, to prevent damage to the healthy cells, neurons and astrocytes, we selected a specific 'promotor', a piece of DNA that causes the therapeutic gene to become activated only in tumour cells, without attacking the other cells, and we replicated the same result as seen in the first in vitro tests".

Gene therapy is based on the insertion of ad hoc genes into a host cell's genome so that these genes can function inside the cell by borrowing its genetic machinery. How is a bit of genetic code added to a living cell? Scientists use the mechanisms naturally adopted by viruses. Viruses are strange entities: although they have their own genome, they are not able to duplicate, and reproduce, by themselves. For this reason they sneak into cells, and insert their own DNA into the host genome, so that the cell starts working for them by duplicating their genes as well and forming other viruses. "By making the virus harmless, that is, by emptying the shell containing its genome and filling it with therapeutic genes, we can add new genes, or enhanced versions of endogenous genes, to the host cell", explains Falcone.

So that is precisely what Mallamaci and colleagues did: they introduced a particularly active version of Emx2 into the tumour cells. The results so far have been unequivocal and have demonstrated that Emx2 is able to kill the cells of at least four different types of glioblastoma, both in vitro and in vivo in rodents, without damaging the healthy cells of nervous system. Since they also observed that the treatment targeted may points of the tumour process, there are good chances of effectively contrasting the development of aggressive recurrences. "For these to form, there has to be a process of selection of the strongest tumour cells. By targeting them at a variety of different points, we raise the standards in this selection process and - hopefully - we prevent the recurrences", concludes Mallamaci. "Now we plan to extend the in vivo tests to other glioblastomas. With a lot of hard work and a bit of luck we hope that in a few years' time all this can translate into a tangible benefit for the unfortunate patients afflicted by this disease".
-end-


International School of Advanced Studies (SISSA)

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

The Cancer-Fighting Kitchen, Second Edition: Nourishing, Big-Flavor Recipes for Cancer Treatment and Recovery
by Rebecca Katz (Author), Mat Edelson (Author)

This new and revised edition of the IACP award-winning cookbook brings the healing power of delicious, nutritious foods to those whose hearts and bodies crave a revitalizing meal, through 150 new and updated recipes.

Featuring science-based, nutrient-rich recipes that are easy to prepare and designed to give patients a much-needed boost by stimulating appetite and addressing treatment side effects including fatigue, nausea, dehydration, mouth and throat soreness, tastebud changes, and weight loss. A step-by-step guide helps patients nutritionally prepare for all phases of... View Details


Anticancer: A New Way of Life
by David Servan-Schreiber MD PhD (Author)

The revolutionary, New York Times bestselling guide to the powerful lifestyle changes that fight and prevent cancer—an integrative approach based on the latest scientific research
 
“A common-sense blueprint for healthy living.” —Chicago Tribune
 
“Resonating with cancer support communities and recommended nationwide.” —Los Angeles Times
 
“Life affirming . . . filled with practical advice.” —The Seattle Times
 
David Servan-Schreiber was a rising... View Details


The Truth about Cancer: What You Need to Know about Cancer's History, Treatment, and Prevention
by Ty M Bollinger (Author)

Cancer touches more lives than you may think. According to the World Health Organization, one out of three women alive today, and one out of two men, will face a cancer diagnosis in their lifetime.

To Ty Bollinger, this isn’t just a statistic. It’s personal. After losing seven members of his family to cancer over the course of a decade, Ty set out on a global quest to learn as much as he possibly could about cancer treatments and the medical industry that surrounds the disease. He has written this book to share what he’s uncovered—some of which may shock you—and to give you... View Details


Tripping over the Truth: How the Metabolic Theory of Cancer Is Overturning One of Medicine's Most Entrenched Paradigms
by Travis Christofferson (Author), Dominic D'Agostino (Foreword)

With a new foreword by Dr. Dominic D'Agostino, PhD and epilogue by the author

 A masterful synchronization of history and cutting-edge science shines new light on humanity's darkest diagnosis.

In the wake of the Cancer Genome Atlas project's failure to provide a legible roadmap to a cure for cancer, science writer Travis Christofferson illuminates a promising blend of old and new perspectives on the disease. Tripping over the Truth follows the story of cancer’s proposed metabolic origin from the vaunted halls of the German scientific golden age to... View Details


Cancer: 50 Essential Things to Do: 2013 Edition
by Greg Anderson (Author)

The ground-breaking classic guide to surviving cancer?now completely updated!

Revised and updated for the first time since 1999, this invaluable guide to cancer recovery offers an easily accessible plan for patients and family members. Written by a cancer survivor, the book is an inspiring, action-oriented roadmap for those who choose to adopt a stance of hope and take charge of their diagnosis.

With penetrating insights that bring together more than two decades of scientifically supported research and experience, Anderson reveals a step-by-step holistic action plan... View Details


Living with Cancer: A Step-by-Step Guide for Coping Medically and Emotionally with a Serious Diagnosis (A Johns Hopkins Press Health Book)
by Vicki A. Jackson (Author), David P. Ryan (Author), Michelle D. Seaton (Author)

The prospect of entering treatment is overwhelming for anyone facing a diagnosis of cancer. While patients have access to a vast amount of medical information online, this advice is often unreliable or confusing. In Living with Cancer, Drs. Vicki A. Jackson and David P. Ryan have crafted the first step-by-step guide aimed at helping people with this life-defining disease grasp what’s happening to them while coping physically and emotionally with cancer treatment.

An empathetic resource full of relatable patient stories, this book teaches patients and caregivers how to ask... View Details


Cancer Hates Tea: A Unique Preventive and Transformative Lifestyle Change to Help Crush Cancer
by Maria Uspenski (Author), Dr. Mary L. Hardy (Foreword)

Drink Tea to Tell Cancer ‘Hit the Road’

Become a tea lover with a purpose and help your body defend itself against cancer. Learn to embrace tea in all its varieties― green, white, black, pu-erh, herbal and more―as both a mental and physical experience to protect your health. Discover the history, growing information and health implications of each variety, as well as uniquely delicious methods to boost your intake with serving suggestions, food pairings and recipes that highlight the benefits of tea.

After her own battle with cancer, Maria Uspenski extensively... View Details


F*ck Cancer: A totally inappropriate self-affirming adult coloring book (Totally Inappropriate Series) (Volume 4)
by Jen Meyers (Author)

*A portion of the proceeds from this book will be donated to support research dedicated to finding a cure for cancer. Because fuck cancer.

This book is for you.

If you are fighting cancer, this is for you. If your brother, sister, mom, dad, son, daughter, relative, or friend is fighting cancer, this is for you. If you've lost someone to cancer like I have, this is for you. If cancer affects your life in any way, this is for you.

The stress of cancer can feel crushing. But perhaps this book can help you get away from it all, if only for a little... View Details


Anti-Cancer Smoothies: Healing With Superfoods: 35 Delicious Smoothie Recipes to Fight Cancer, Live Healthy and Boost Your Energy
by Linda H. Harris (Author)

Anti-Cancer Diet, Cancer Fighting Foods, and Cancer Nutrition

Whether you have cancer or you're at risk of cancer because of your family history - the way you eat can have a major impact on your health and your ability to fight or manage your disease. Cancer is notorious for sapping the strength and nutrition out of a person's body. You'll need to replace a lot of the vitamins, nutrients and minerals that certain drugs and treatments deplete.

The Anti-Cancer Smoothies in this book are made of healthy and tasty vegetables, fruits, spices and herbs that are known to fight cancer.... View Details


Beating Cancer with Nutrition (Fourth Edition) Rev
by Patrick Quillin (Author)

There is good news in the "war on cancer". Optimal nutrition coupled with appropriate medical treatment can dramatically improve the quality and quantity of life and chances for a complete remission for most cancer patients. A well-nourished cancer patient can better manage the disease. Cancer is the number two cause of death in America and the developed nations of the world with one out of four dying from cancer and 38% of women and 43% of men projected to develop cancer over their lifetime. While the overall death rate from cancer has not appreciably declined since... View Details

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Simple Solutions
Sometimes, the best solutions to complex problems are simple. But simple doesn't always mean easy. This hour, TED speakers describe the innovation and hard work that goes into achieving simplicity. Guests include designer Mileha Soneji, chef Sam Kass, sleep researcher Wendy Troxel, public health advocate Myriam Sidibe, and engineer Amos Winter.
Now Playing: Science for the People

#448 Pavlov (Rebroadcast)
This week, we're learning about the life and work of a groundbreaking physiologist whose work on learning and instinct is familiar worldwide, and almost universally misunderstood. We'll spend the hour with Daniel Todes, Ph.D, Professor of History of Medicine at The Johns Hopkins University, discussing his book "Ivan Pavlov: A Russian Life in Science."