Researchers Want to Regulate Your Genes to Help You Defeat Cancer

Getting the Code Treatment

Molecular insight into our own DNA is now possible, a field called personal genomics. Such approaches can let us know when we might have cancer-causing alterations in our genes. Well-known examples are the melanoma oncogene BRAF kinase, the breast cancer gene BRCA1 and the prostate specific antigen PSA. The Conversation

But there is more to cancer and other diseases than our genes. In addition to the DNA code, there is a hidden layer of regulation controlling the activity of genes – while not changing the DNA itself. This field, called epigenetics, is the study of how genes are regulated to express themselves, even though they rely on the same genetic information. A gene is still a gene, but it responds differently to many facets of its chemical environment.

For example, have you thought about why identical twins are different? How it is possible that the lifestyle of our grandparents can affect our lives today? Something beyond our DNA is at work. This is epigenetics.

The hidden layer responsible for fine-tuning alongside our DNA is called epigenomic regulation. Epigenomics is the field of quantifying epigenetic marks on a genome-wide scale, thereby capturing a snapshot of our epigenetic state.

Recently, the systems biology and cancer metabolism lab at UC Merced published discoveries about an epigenetic factor called Jumonji. This factor not only affects how an entire network of cancer genes behaves; it actually takes on the role of a cancer gene, bringing uncontrollable cell growth.

Epigenomics Captures How Gene Activity Is Controlled

Already, doctors and others who diagnose diseases can, to some degree, use personal genomics tests that integrate our unique genetic makeup into clinical decision-making. However, there is more to our genome than what such tests can reveal.

Epigenetics makes sense of chemical modifications that can switch genes on or off. Importantly, none of these modifications changes the DNA sequence. Alternatively, our own cells use epigenomic regulators to control the activity of genes. If the right chemistry is in place, the right gene products are expressed at the right time.

Environmental influences like nutrition or cigarette smoke as well as our own hormones have strong epigenetic impact and affect how active our genes are.

In a disease such as cancer, epigenomic regulators such as Jumonji are often mistuned, causing them to affect gene activity. One thing they may do is to fail to put the right chemical modifications on their target genes, which rely on many factors to switch their activity on or off. This can lead to altered metabolism, which promotes unlimited cellular growth. Once cells have unlimited ability to divide, a tumor forms.

The researchers found that Jumonji is overabundant in cancer cells and promotes uncontrolled division of cancer cells, which leads to unstoppable tumor growth. Jumonji takes the role of an epigenetic master regulator of cancer genes.

In addition, Jumonji teams up with hormone-dependent regulators that are responsible for treatment-resistant cancers.

Systems biologists can help to understand how we can overcome resistances. Systems biology opens possibilities to understand regulatory signals and circuits that govern our cells. If we are able to comprehend these signals, we can design drugs to break unwanted circuits and overcome resistances. Given its hidden, complex nature, epigenomics benefits from a systems biology approach that lays open critical wiring of our cells.

Toward Personalized Epigenomics

Epigenomics has a lot of promise for cancer treatments, but there are still many more questions that we need to answer. What does the epigenome of a healthy person look? And how does the epigenome change as we age? How does the epigenome of a sick person differ? In the future, these important questions will be addressed by personalized epigenomics, which tries to extract information out of a comprehensive picture of a person’s epigenome.

You may ask: Why can we not create a simple test that tells us if we have good genes but an unfavorable epigenome?

Our epigenome is highly dynamic. Epigenomic regulators are nonstop at work, including Jumonji, removing or adding chemical marks allowing for transient gene readouts while blocking it in the next minute.

Is it too early for consumers to think about personalized tests? Is the information still too cryptic or too unreliable to draw conclusions?

Personal gene tests for cancer exist. Hollywood actor Ben Stiller claims a simple genetic test for abnormally high levels of the prostate antigen saved his life.

Abnormally high levels of the prostate specific antigen in the blood can mean that a man has prostate cancer, but not always. That is why the test is not FDA-approved. And this test does not take epigenetic factors into account.


Artistic illustration of an epigenomic handprint capturing regulation of a person beyond changes in DNA. In background research campus with art statue ‘New Beginnings,’ symbolizing hope for cure. Credit: Systems Biology and Cancer Metabolism Laboratory, Fabian V. Filipp

Cancer Drugs Against Epigenomic Factors Promise Hope

Drugs targeting the epigenomic machinery raise optimism as a viable direction of clinical research. Present-day clinical questions relevant to epigenetic research address which drug molecules modify the epigenome and which specifically kill cancer cells. It is open whether epigenetics is on the good or on the bad side of cancer. Researchers found that epigenetics can even assist the cancer cells to manipulate our own immune system and to evade the drug targeting approaches.

According to recent genomic insights, researchers compare the delicate equilibrium to Yin and Yang, complementary forces that keep each other in check. If one force overtakes the systems, it is out of equilibrium. For the cells this means either unlimited growth, cancer or death. Without doubt, once we have a better understanding of epigenetic regulation, we can design drugs that counterregulate these factors.

This is beginning to happen with some cancers. Recent breakthroughs in melanoma research identified a genetic mutation of an epigenetic player. Cancer resistance to treatment is a major obstacle. However, epigenetic drugs, on their own or in combination with other drugs, can be a viable alternative.

The epigenetic drug used in the laboratory study stops the ability of cancer cells to hide from the immune system and makes the tumor vulnerable. For cancer patients with epigenetic activation, epigenetic drugs promise hope.


Fabian V. Filipp, Assistant Professor of Systems Biology and Cancer Metabolism, University of California, Merced

This article was originally published on The Conversation. Read the original article.The Conversation

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Drug-Delivering “Mecha-Sperm” May Be the Future of Cancer Treatment

Killer Sperm

Humanity’s battle with cancer has goaded us to turn to some of the most unconventional therapies possible in hope of combating the deeply emotional and turbulent disease. Physicians are prescribing electric caps like the Optune to zap tumors away, while others are suggesting the analysis of a quick breath can detect cancer. There might be something a little bit more unorthodox  on the horizon to tackle cancer: physician scientists from the Institute of Nanosciences in Germany claim the answer may be human sperm.

Mariana Medina-Sánchez and her team led a study looking into the unique drug delivery benefits human sperm could provide. The team noticed that when sperm are submerged in an active ingredient found in cancer treating drugs, it can absorb large doses. The sperm can then be assembled into microscopic mechanical harnesses, creating sperm-hybrid micromotors. The iron in these harnesses allows clinicians to manipulate the direction of the sperm with external magnetic fields, which in turn allows doctors to direct the drug-coated sperm in the direction of the tumor.

Once the metal harness reaches a surface, its quick release system relinquishes its grip on the sperm’s and allows them swim away once they reach their target. In theory, this would enable the sperm to burrow deeper into tumor tissue, exposing more cancer cells to the drugs in a more direct way than has been possible by other current treatments.

While Medina-Sánchez’s team has only experimented with bull sperm (as they are similar in size to human sperm) the team noticed that the sperm-hybrid micromotor reduced cancerous cells by 87% in just 72 hours. The method proved to be far more effective than treating cancer cells with the drugs alone.

Revolutionizing Drug Delivery

The sperm-hybrids could be potentially advantageous for the hundreds of thousands of women with gynecological cancers, and perhaps even other diseases of the female reproductive tract. The sperm-hybrid micromotor boasts significant advantages: not only do sperm cells provide added protection when it comes to keeping the drug from degrading prematurely. They also wouldn’t unnecessarily trigger the immune system, like a drug piggybacking on bacteria would.

Drug delivery comes in many forms: swallowing, inhalation, absorption through the skin, or intravenous injections. That being said, it’s not surprising that nanotechnology is a hot topic in drug delivery. Even with new technologies, science seems to have stagnated around several central topics: delivering drugs past the blood-brain barrier, enhancing individual cellular delivery, and combining diagnostics and treatments.

Chemotherapies that inadvertently target non-cancerous cells result in the death of normal cells. This is a consequence that can be avoided if Medina-Sánchez’s sperm-hybrid micromotors are approved by national standards.

While Medina-Sánchez’s new approach does have many questions to left to answer — including how sperm could be introduced into the reproductive system as drug-delivery agents while not also potentially causing pregnancy — the method certainly seems promising.

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The FDA Is Moving From Animal Testing To “Organs-On-Chips”

Chip Testing

Testing on animals has been an important and integral part of advancing medicine for ages. In order for a new drug to get approval to be tested in humans, the Food and Drug Administration (FDA) requires that it be tested in animals first. However, while animal testing can indicate whether a drug may or may not be harmful if introduced into a human, it’s difficult to guarantee that any results gleaned from animal testing would translate to people. There are also the moral implications of testing on animals to consider.

Bioprinting: How 3D Printing is Changing Medicine
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However, a recent move by the FDA puts us on the path to cutting out that middle man, removing animals from the testing picture altogether.

Yesterday, the agency announced it will begin working with Emulate, a company that devised “organ-on-chip” technology that lives up to the company’s name by emulating organ function on a device smaller than a human thumb. The idea is to test drugs on these chips to obtain results more accurate than could be gleaned from animal testing or even cells cultured from humans.

Saving Lives All Around

To being, the FDA will center the collaboration around the company’s liver chips. The liver is a vital organ to medicine as it is where most drugs get broken down, so it makes sense to start there. However, according to the company’s site, “Our team has developed working models of the lung, liver, intestine, and skin. We are also developing designs for other organ systems such as the kidney, heart, and brain,” so if the liver trials go well, we might be seeing future expansion to other chips.

Photo source: Emulate Inc.
Photo source: Emulate Inc.

This program will not stop all animal testing, at least not at first. But this collaboration does allow for a unique opportunity to continue to save human lives, all while sparing the lives of animals that may have otherwise existed to live and die for science.

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Your Brain Cells Could Be Reprogrammed to Fight Parkinson’s Disease

Support Cells Turned Super Cells

Parkinson’s disease is one of the world’s most common neurodegenerative ailments. It causes patients with Parkinson’s to lose dopamine neurons, which are important for the motor control centers of the brain. According to statistics from the Parkinson’s Disease Foundation, there are over 10 million people worldwide who suffer from it, with about 60,000 diagnosed cases in the United States alone.

Researchers from the the Karolinska Institute in Stockholm developed a stem cell-based treatment that doesn’t rely on embryonic or adult stem cells, which are often too difficult to harness and transplant into the brain. Instead, they found a way to reprogram the brain’s astrocytes — support cells for neurons — into dopamine neurons.

“You can directly reprogram a cell that is already inside the brain and change the function in such a way that you can improve neurological symptoms,” senior author Ernest Arenas explained to the Scientific American.

The trick was adding a cocktail of three genes and a small RNA molecule to force astrocytes into becoming dopamine neurons. The treatment was tested on mice whose dopamine neurons in brain were destroyed to simulate Parkinson’s disease. Within five weeks of being injected with this gene cocktail, the mice showed improved and more coordinated movement. These results were published in the journal Nature Biotechnology.

A Novel Approach

While this stem cell approach won’t cure Parkinson’s, it can certainly improve current standard treatments for it. For one, astrocytes are already present in the brains of Parkinson’s patients. Reprogramming these would eliminate the need for donor cells, which run the usual incompatibility risks associated with transplants. Second, the proteins produced in the treatment are involved in normal cellular processes, limiting potential side effects that current drug-based therapies often carry.

“This is like stem cell 2.0. It’s the next-generation approach to stem cell treatments and regenerative medicine,” said James Beck, VP and chief scientific officer for the Parkinson’s Disease Foundation, a nonprofit organization that was not involved with the research.

Still, there’s a long way to go before an actual cure can be developed. “Motor improvement is only half the battle,” Beck said to Scientific American. But winning half the battle is still significant. This new approach, he noted, could ease the management of motor symptoms in potentially millions of Parkinson’s patients. It might also make keeping up with medications simpler for them, potentially reducing the eight or more pills that patients with advanced Parkinson’s often take.

Further research is needed to make sure that this reprogramming method doesn’t change other cells in the brain. Only then would it be ready for human clinical trials. But Beck is hopeful that this study will spur new Parkinson’s treatments down the road. “This is an insight into what the future of Parkinson’s treatment holds,” Beck noted.

Stem cell therapies are revolutionizing Parkinson’s disease treatment, as well as a host of other medical conditions. Many believe that the ability to reprogram cells is a glimpse of the future, not just of Parkinson’s treatment, but of the entire field of medical research.

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Zero-G Space-Based Factories May be The Future of Our World

Mission: Manufacturing

SpaceX has been getting a lot of attention since its historic launch of recycled rockets. The cost of getting people and technology into space has never been cheaper. This is opening up an entirely new world of possibilities for companies across a variety of different fields. One surprising development coming out of this news is an increased interest in manufacturing in space.

There are a lot of benefits of moving operations to space that can significantly benefit certain types of manufacturing. Space offers the closest physical approximation to a vacuum (something that is impossible on Earth), solar power only limited by what’s collecting it, extreme temperatures, and perhaps most importantly, microgravity. These factors can expand the capability of what manufacturers could accomplish on Earth. Companies are already vying to be among the first to be granted the opportunity to create in space, with exciting prospects across a variety of fields — especially in medicine.

The makers of a revolutionary stem cell printer, nScrypt, are working with two other companies, Bioficial Organs, and Techshot to begin printing real hearts from patients’ stem cells on the International Space Station (ISS) by 2019.

3D printing hearts in this way is not entirely possible on Earth. Researchers have to devise a scaffolding onto which the material can be printed, but it then must dissolve or be removed without damaging the printed structure. However, it is possible to print without a scaffold in space. “If we try to do it on Earth, it would look pretty for about a second and then just kind of melt all over the table,” says Eugene Boland, chief scientist at Techshot. “It would look like you just poured a Jell-O mold and then tried to immediately serve it—it would glob on your plate into this gelatinous mess.”

Space Organs

As you may have seen, most 3D printing needs to be done in layers. The object is built from the ground up one (effectively) 2-dimensional layer at a time. In space, the lack of gravity allows objects to actually print in 3D. Not only that, but the speed of the printing could be up to 100 times faster. For example, the gravity aboard the ISS will allow the printed structure to retain its shape as stem cells work to grow the tissue of a transplantable heart. The hearts could be ready in as little as 45 days. With the average median wait time of a heart transplant being four months in the United States, printing in space could save countless lives.

“People are getting tired of seeing Yoda figures being printed,” says nScrypt CEO Kenneth Church. “They’re saying ‘You promised me a heart. Where is it?’ And what I’m going to tell you is, ‘It’s in space.’”

Manufacturing in space isn’t limited to just saving lives either: more efficient fiber optics cables and solar panels are possible when they are made in space. The future of manufacturing is launching toward the stars, it is clear that even the sky is no longer the limit.

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New Artificial Organ Can Be Implanted in the Body to Create Cancer-Fighting Cells

Artificial Thymus

Many artificial organs are being developed as an alternative to donated organs, which are only temporary solutions that require the recipients to maintain a lifetime regiment of medications. With recent advancements in biomedical technologies, the time may be coming when those who require transplants no longer need to wait on donation lists to replace organs like kidneys and blood vessels. And now, scientists have added the thymus to the list of body parts we can artificially simulate.

The thymus is a gland that is essential to your immune system. T cells, a type of white blood cell that helps to get rid of viruses, bacterial infections, and cancer cells, mature within this gland. When people get sick (or as they age), the thymus becomes worse at its job. In some cases, people with different types of cancer are not getting the biological support and help they need from their T cells.

Now, there are adoptive T cell immunotherapy treatments which involve removing T cells from a patient, “fixing” them, and transfusing them back. But these treatments depend on the patient actually having enough of these cells, and many do not. This type of treatment also takes a very long time to complete.

To create a more sustainable and effective solution to this serious medical issue, researchers at UCLA created artificial thymic organoids that create T cells from blood stem cells. This was an incredible feat in medical science — but could these artificial structures create specialized T cells that have cancer-fighting receptors? Yes.

Life Saving

The team inserted a Gene for cancer-fighting receptors into blood stem cells. This caused the organoids to produce only cancer-specific T cells. Because other types of T cells could accidentally target and attack healthy tissue, these results are exceptionally positive. If specific T cells can be created and other types turned off, cancer cells can be targeted and attacked without causing autoimmunity problems.

The researchers published their work in Nature Methods and are now investigating this technique with pluripotent stem cells. This could allow for the creation of a more sustainable supply of these life-saving cells. The team is calling on other scientists to reproduce its work.

An Exponential Timeline of Organ Transplants
Click to View Full Infographic

This new development could be one large step towards reducing the costs of cancer treatments. It is no secret that most modern cancer treatments are either extremely costly, dangerous to healthy tissues, not effective enough, or a combination of these. There are many treatments that successfully put patients into remission and allow them to continue on with healthy and fulfilled lives. But, there is still a lot of room for improvement, and this could be one of them.

Although this patented artificial structure will have to go through years of clinical trials before it can be widely adapted by the medical community, and it has not been tested in humans yet, it holds promise as a way to guarantee the creation of healthy cancer-targeted T cells. The availability of treatment may not depend on a patient’s existing cells that must be removed and engineered. Instead, patients of varying levels of illness could have equal access to treatment — and to hope.

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