Cancer Research: Study,find ways to target rare tumor ♦ Intelligent gel attacks cancer ♦ Personalized drug screening on horizon for multiple myeloma patients

Researchers identify a new mode of drug resistance to emerging therapies in prostate cancer Advanced prostate cancer is a disease notoriously resistant to treatment. New research sheds light on a new mode of drug resistance to emerging therapies in metastatic prostate cancer. This discovery ultimately may help predict which patients may benefit most from treatment

New model to study, find ways to target rare tumor Angiosarcoma or lymphangiosarcoma, a rare malignant tumor of the blood or lymphatic vessels, has no cure, say cancer researchers. However, through recent study, a team has found a new target that could lead to therapies for this rare type of tumor.

Intelligent gel attacks cancer A new injectable “bio gel” is effective in delivering anti-cancer agents directly into cancerous tumours and killing them. This technology has already been successfully tested in the laboratory. If it works in patients, the therapy could one day revolutionize treatment for many forms of cancer

Personalized drug screening on horizon for multiple myeloma patients A personalized method for testing the effectiveness of drugs that treat multiple myeloma may predict quickly and more accurately the best treatments for individual patients with the bone marrow cancer. The process also may aid patients with leukemia or lymphoma

Pulmonary Research: Treating pulmonary diseases using Alaska pollock gelatin ♦ White blood cells guards against tumor lung metastasis ♦ New study explores how anxiety can aggravate asthma

A subpopulation of white blood cells guards against tumor lung metastasis Among foot soldiers on the immune front line is a subpopulation of white blood cells called “patrolling monocytes,” whose job is to cruise the bloodstream, cart off cellular debris, and block invasion of a less benign population of inflammatory cells. Now, a study illustrates that patrolling monocytes may also play an anti-cancer role, particularly in the lung.
Lung cancer surgery can be beneficial for high-risk patients with early stage disease

Surgical lung resection, in which part of a lung is removed, can be a safe and effective treatment option for high-risk patients with early stage lung cancer,

New study explores how anxiety can aggravate asthma A new study involved mimicking asthma symptoms to see how anxiety sensitivity affected asthma sufferers. The researchers recruited 101 college undergraduates who reported having asthma. The experiment aimed to mimic asthma symptoms by having study participants breathe in-and-out through a narrow straw, about the width of a coffee-stirrer straw.
Treating pulmonary diseases using Alaska pollock gelatin In recent years, patients with pulmonary emphysema have been increasing mainly among middle-aged and elderly males due to aging and excessive smoking. Emphysema makes brittle lungs, and in severe cases, holes develop in the lung tissue, causing air leakage. Researchers have developed a new sealant to close holes developed in lungs and blood vessels using Alaska pollock gelatin, and have reported that the sealant is about 12 times stronger than conventional sealants.

Cancer Research: Heat-activated ‘grenade’ to target cancer ♦ Predicting cancer's growth from few clues ♦ Brain tumor-shrinking molecules

Heat-activated ‘grenade’ to target cancer Researchers have developed cancer drug-packed ‘grenades’ armed with heat sensitive triggers, allowing for treatment to be targeted directly at tumors.

New computational strategy finds brain tumor-shrinking molecules Patients with glioblastoma, a type of malignant brain tumor, usually survive fewer than 15 months following diagnosis. Since there are no effective treatments for the deadly disease, researchers developed a new computational strategy to search for molecules that could be developed into glioblastoma drugs. In mouse models of human glioblastoma, one molecule they found shrank the average tumor size by half.

Predicting cancer's growth from few clues Duke mathematicians are developing ways to help doctors predict how different cancers are likely to progress when measurements of tumor growth are hard to come by. In a new study, they describe a way to compare common models of tumor growth, using only two time-point measurements of tumor size -- often the maximum available before patients begin treatment. Determining which models work best for different cancers is key to designing optimum treatment strategies.

Cancer cells use secret tunnels to communicate, smuggle cancer signals their neighbors Cancer cells use previously unknown channels to communicate with one another and with adjacent non-cancerous cells, a new report suggests. The researchers report that an in vitro co-culture system robustly quantifies the transfer of fluorescent proteins between cells and can also compare between various conditions

Breast Cancer Tumor Test to Tailor Treatments

Breast cancer is the second most common cancer in U.S. women (after skin cancer). Many women with early-stage breast cancer are advised to receive chemotherapy in addition to radiation and hormonal therapy. However, it isn’t necessary to treat all breast cancer with chemotherapy, which can also be costly, toxic, and inconvenient.

The death rate from breast cancer has dropped steadily over the past 20 years, but breast cancer is still the second leading cause of cancer-related death in U.S. women. Image Credit: Ryan McVay/Photodisc/Thinkstock.

An international team of researchers has been exploring ways to identify which tumors would be the most likely to benefit from chemotherapy. From April 2006 to October 2010, the scientists enrolled more than 10,000 women from around the world in a large clinical trial sponsored by NIH’s National Cancer Institute (NCI).The women, ages 18 to 75, had recently been diagnosed with a specific type of breast cancer: hormone-receptor positive, human epidermal growth factor receptor type 2 (HER2) negative that hadn’t spread to the lymph nodes.

Many women with this type of breast cancer can likely be adequately treated with hormone therapy alone. However, it’s been difficult to identify the women who could safely avoid adjuvant chemotherapy, which is given after the primary therapy to reduce the risk of metastases and thus increase the chance of long-term cancer-free survival.

The scientists explored the ability of a diagnostic gene test, the Oncotype DX Recurrence Score (Genomic Health, Inc.), to predict which women could safely avoid receiving chemotherapy. The test had previously been found, using retrospective analyses (which look back at past events), to help predict the usefulness of chemotherapy and the likelihood of distant breast cancer recurrence. The test works by analyzing RNA from tumor samples for the presence of 21 genes. Based on the results, tumors are graded on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence.

This prospective study (looking forward, following the women over time) was led by Dr. Joseph A. Sparano of Montefiore Einstein Center for Cancer Care and Albert Einstein College of Medicine. Results were published online on September 28, 2015, in the New England Journal of Medicine.

The team found that 1,626 of the women (16%) had a recurrence score of 0 to 10, indicating a very low risk of recurrence. These women were assigned to receive standard hormone therapy such as tamoxifen or aromatase inhibitors, but didn’t undergo chemotherapy. At 5 years of follow-up, their risk of recurrence of breast cancer at a distant site was less than 1%, and the risk of any recurrence was less than 2%. The women had an overall survival rate of 98%.

These results show that the Oncotype DX test can clearly identify women with an early stage of this type of breast cancer who can safely avoid chemotherapy. However, nearly 70% of the participants had a mid-range score of 11 to 25. These women were randomly assigned to receive endocrine therapy plus chemotherapy or endocrine therapy alone, and are still being monitored. Scientists continue to work on other diagnostic gene test as well.

—by Carol Torgan, Ph.D.

Cancer Research: A new virus in liver cancer ♦ Tumour suppressor genes curb growth in neighboring cells ♦ Researchers thwart cancer cells by triggering 'virus alert'

A new virus in liver cancer More than a cause of a simple infection, viruses are often involved in the development of serious diseases. Such is the case with liver cancer, which often develops in an organ that has been weakened by hepatitis B or C virus. Researchers have just identified the role of a new virus, hitherto unsuspected, in the occurrence of a rare type of liver cancer.

New strategy improves detection of genetic mutations in hereditary colorectal cancer Enhanced accuracy and reduced turnaround time of testing can provide vital information for patients suspected of having lynch syndrome and their family members, according to a new report.

New synthetic tumor environments make cancer research more realistic Tumors are notoriously difficult to study in their natural habitat -- body tissues -- but a new synthetic tissue environment may give cancer researchers the next-best look at tumor growth and behavior. Researchers have now developed a new technique to create a cell habitat of hydrogels which can realistically and quickly recreate microenvironments found across biology.

Tumor suppressor genes curb growth in neighboring cells Researchers have unraveled a role for tumor suppressor genes in restricting the growth of neighboring cell populations. The study might have implications for understanding the early events of tumorigenesis and the selection of the tumour-initiating cells.

Researchers thwart cancer cells by triggering 'virus alert' Working with human cancer cell lines and mice, researchers have found a way to trigger a type of immune system 'virus alert' that may one day boost cancer patients' response to immunotherapy drugs. An increasingly promising focus of cancer research, the drugs are designed to disarm cancer cells' ability to avoid detection and destruction by the immune system.

Cancer Research; Long-term NSAID use may reduce colorectal cancer risk ♦ Divide and rule: A tumor's strategy ♦ Imaging software could speed up breast cancer diagnosis

Imaging software could speed up breast cancer diagnosis New software could speed up breast cancer diagnosis with 90 percent accuracy without the need for a specialist. This could improve breast cancer management, particularly in developing countries where pathologists are not routinely available.

Divide and rule: A tumor's strategy Researchers have discovered how aggressive cells can invade healthy tissue during the earliest stage of tumor development. This opens up new ways of attacking cancer at its root, they say

Light/moderate drinking linked to increased risk of some cancers in women, male smokers Even light and moderate drinking (up to one drink a day for women and up to two drinks a day for men) is associated with an increased risk of certain alcohol related cancers in women and male smokers.

Electronic trigger reduces delays in evaluation for cancer diagnosis Electronic triggers designed to search for key data, developed by researchers at Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, were able to identify and reduce follow-up delays for patients being evaluated for a diagnosis of colon or prostate cancer.

Long-term NSAID use may reduce CRC risk Long-term, continuous use of low-dose aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with decreased colorectal cancer risk. The findings of a population-based, case-control study.

Cancer Research: Watching a tumor grow in real-time ♦ Urine test for early stage pancreatic cancer possible ♦ PHD2 oxygen sensor inhibits breast cancer dissemination

Watching a tumor grow in real-time Researchers have gained new insight into the phases of breast cancer growth. The ability to visualize and characterize the composition of a tumor in detail during its development can provide valuable insights in order to target appropriate therapeutics.

Cancer patients lose faith in health care system if referred late by GP If it takes more than three trips to the GP to be referred for cancer tests, patients are more likely to be dissatisfied with their overall care, eroding confidence in the doctors and nurses who go on to treat and monitor them.

Blocking PHD2 oxygen sensor inhibits breast cancer dissemination Reducing the expression of the PHD2 oxygen sensor impairs the ability of breast cancers to metastasize (spread) to other parts of the body, scientists have discovered. Breast cancer is the second leading cause of cancer death in women, primarily due to metastasis. These findings indicate that PHD2 inhibition may have valuable therapeutic potential.

Urine test for early stage pancreatic cancer possible after biomarker discovery A combination of three proteins found at high levels in urine can accurately detect early-stage pancreatic cancer, researchers have found. The discovery could lead to a non-invasive, inexpensive test to screen people at high risk of developing the disease.

Health Research: Stem cells provide lasting pain relief in mice ♦ New compounds may treat depression rapidly with few side effects ♦ Skin cancer marker plays critical role in tumor growth

Elective surgery is associated with lower risk of death than drugs for ulcerative colitis treatment

Patients over 50 with ulcerative colitis (UC), a chronic disease of the colon, who undergo surgery to treat their condition live longer than those who are treated with medications.

Stem cells provide lasting pain relief in mice

Researchers have identified a promising stem cell based-therapy to address the chronic pain that affects more than one-third of the US adult population. In mice, bone marrow stromal cells were found to provide lasting relief for chronic pain caused by nerve damage. The findings also may advance cell-based therapies in chronic pain conditions, lower back pain and spinal cord injuries.

New compounds may treat depression rapidly with few side effects

A new study has identified promising compounds that could successfully treat depression in less than 24 hours with few side effects. The compounds could offer significant advantages over current antidepressant medications.

Skin cancer marker plays critical role in tumor growth

The protein keratin 17 -- the presence of which is used in the lab to detect and stage various types of cancers -- is not just a biomarker for the disease, but may play a critical role in tumor growth, scientists suggest.

New surgical technique preserves kidney function following tumor removal

Renal cell carcinomas are one of the most common types of cancer. In order to preserve its wide range of functions, every effort is made not to remove the entire kidney, but rather just a portion of it. A surgical method that preserves long-term renal function has now been carried out successfully.

Cancer Research: How the tumor escapes the immune response ♦ Treating breast cancer with progesterone could aid survival ♦ Cancer drug 49 times more potent than Cisplatin

Cancer drug 49 times more potent than Cisplatin A new cancer drug has been found to have effectiveness for ovarian and bowel cancer that is 49 times as potent as Cisplatin. The key to this new drug, researchers report, is that it can shut down a cancer cell's metabolism. They add that the new drug could be cheaper to produce and less harm to healthy cells than alternative therapies.

Breast cancer routinely over diagnosed in Norway For every life saved by Norway's Breast Cancer Screening Program, five women are over diagnosed, and have to go through an operation to remove a tumor that otherwise never would have caused problems.

Disrupting cells' 'powerhouses' can lead to tumor growth A  study implicates defects in mitochondria, the energy-production centers of cells, as playing a key role in the transition from normal to cancerous. In their report, researchers note that looking for defects in cytochrome oxidase C could be a biomarker for cancer screening.

Treating breast cancer with progesterone could aid survival A special technique where breast cancer cells are “rescued” for research has been developed by researchers. Coupled with advanced scientific technologies, this has provided a unique insight into the hormone regulation of breast cancers, which is expected to lead to new treatments for the disease.

Lymphoma: How the tumor escapes the immune response Natural killer cells of the immune system can fend off malignant lymphoma cells and thus are considered a promising therapeutic approach. However, in the direct vicinity of the tumor they lose their effect. Scientists have now elucidated which mechanisms block the natural killer cells and how this blockade could be lifted.

Brain Research: New model to study HIV latency in brain cells ♦ Emotional brains 'physically different' from rational ones ♦ New imaging technique could make brain tumor removal safer

Brain injury patterns linked to post-concussion depression, anxiety Post-concussion psychiatric disorders like depression, anxiety and irritability can be extremely disabling for those among the nearly 3.8 million people in the United States who suffer concussions every year. Now, a new MRI study has found distinct injury patterns in the brains of people with concussion-related depression and anxiety

Emotional brains 'physically different' from rational ones Researchers have found physical differences in the brains of people who respond emotionally to others' feelings, compared to those who respond more rationally.

New model to study HIV latency in brain cells Over 35 million people worldwide are currently infected by HIV. Antiviral therapies can keep the virus from multiplying. However, no drug can cure infection so far, because various cell types continue to carry the virus in a latent, i.e. quiescent, state. Scientists have now established a model for latent HIV infection of brain cells. The researchers used this model to identify various compounds that affect latency of the virus in the brain.

Brain receptor found to significantly affect cocaine addiction By manipulating the activity of Activin receptors in the brain, researchers report that they were able to increase or decrease cocaine-taking and relapse behavior in animal models. The study focused on receptors in regions of the brain involved in pleasure and reward.

New imaging technique could make brain tumor removal safer, more effective, study suggests Brain surgery is famously difficult for good reason: When removing a tumor, for example, neurosurgeons walk a tightrope as they try to take out as much of the cancer as possible while keeping crucial brain tissue intact — and visually distinguishing the two is often impossible. Now researchers report they have developed an imaging technology that could provide surgeons with a color-coded map of a patient’s brain showing which areas are and are not cancer.

Cancer Research: Nanotechnology identifies brain tumor types ♦ Tumor surroundings are shown to affect progression ♦ Resistant breast cancer mechanism revealed

Nanotechnology identifies brain tumor types through MRI 'virtual biopsy' A tiny drug-delivery system has been invented that can identify cancer cell types in the brain through 'virtual biopsies' and then attack the molecular structure of the disease. The results could be used to deliver nano-scale drugs that can distinguish and fight tumor cells in the brain without resorting to surgery.

How DNA is organized in our cells A critical role for two proteins in chromatin structure has been uncovered by researchers. Their breakthrough helps explain how DNA is organized in our cells. This discovery could lead to a better understanding of what causes certain types of cancer, such as lymphoma.

Therapy-resistant breast cancer mechanism revealed A cluster of defined, non-coding RNAs are mechanistically involved in endocrine therapy resistance in human breast cancer cells. Furthermore, resveratrol, a kind of polyphenol, was found to repress these RNAs and inhibit the proliferative activity of breast cancer cells which had acquired resistance

Two new, very large classes of RNAs found to be linked to cancer biomark Two new classes of RNAs have been identified that are closely associated with a protein known to be a prognostic biomarker for breast cancer and could play a role in progression of prostate cancer.

Tumor surroundings are shown to affect progression of different cancer subtypes Our environment can have a major impact on how we develop, and it turns out it's no different for cancer cells. A team of researchers reports that two different mouse models of breast cancer progressed differently based on characteristics of the tumor microenvironment -- the area of tissue in which the tumor is embedded.

Health Research: GMO Salmonella promising as anti-cancer therapy ♦ Inactive tumor suppressor gene discovered in lung cancer ♦ New treatment for Barrett's esophagus

New treatment for common digestive condition Barrett's esophagus New research could transform treatments and diagnosis for a common digestive condition which affects thousands of patients.

How gum disease treatment can prevent heart disease  A new study is helping to shed more light on the important connection between the mouth and heart. According to research, scientists have demonstrated that using an oral topical remedy to reduce inflammation associated with periodontitis, more commonly known as gum disease, also results in the prevention of vascular inflammation and can lower the risk of heart attack.

Wristband that measures rest, activity schedule may help predict response to antidepressants A wristband that records motion throughout a 24-hour cycle may be an inexpensive, safe way to determine which patients with major depressive disorder will respond best to commonly prescribed drugs such as Prozac

Inactive tumor suppressor gene discovered in lung cancer The PARD3 gene has been identified by researchers as a tumor suppressor that is inactivated in lung cancer squamous type. PARD3 gene encodes a protein that regulates cell polarization and cell junctions. When the gene is inactivated, errors occur in this cell orientation and in contact with neighboring cells. "Any change affecting this structure promotes tumor development,"

GMO Salmonella promising as anti-cancer therapy Genetically modified Salmonella can be used to kill cancer cells, scientists report. For years, researchers have known that certain strains of bacteria, including Salmonella enterica, can kill cancer cells. Specifically Salmonella enterica Serovar Typhimurium has been shown to not only colonize solid tumors, but also to exhibit an intrinsic antitumor effect. However, in order to use Salmonella as a weapon against cancer in humans, researchers must find a balance between allowing it to kill the cancer and be safe for the patient. This bacteria, commonly known for causing severe food poisoning

Cancer Research: Gold intensifies cancer-killing radiation ♦ Recruiting the entire immune system to attack cancer ♦ New biomarker for uterine cancer discovered

New biomarker for uterine cancer discovered A new biomarker has been discovered that makes it possible to identify women with uterine cancer who have a high risk of recurrence. Endometrial cancer of the uterus is the most common form of gynecologic cancer in Europe and North America. The treatment primarily consists of removing the uterus and in some cases offering chemotherapy if the risk of recurrence is deemed high.

Gold by special delivery intensifies cancer-killing radiation

Researchers have demonstrated what could become a more precise method for targeting cancer cells for radiation. The method would use cancer-seeking peptides to ferry nanoparticles of gold to the site. The gold then helps focus radiation on the cancer cells.

New method to characterize structure of a protein that promotes tumor growth

A new method has been developed to identify a previously unknown structure in a protein called MDMX. MDMX is a crucial regulatory protein that controls p53 -- one of the most commonly mutated genes in cancer.

Recruiting the entire immune system to attack cancer Stimulating both major branches of the immune system halts tumor growth more effectively, new research shows. Orchestrating a successful immune attack against tumors has proven difficult so far, but the new study suggests that such therapies could be improved by simultaneously activating both arms of the immune system. Until now, most researchers have focused on one of two strategies: attacking tumors with antibodies, which activate the innate immune system, or stimulating T cells, which form the backbone of the adaptive immune system.

Cancer Research:Nanoparticles stimulate antitumor response ♦ Risk of developing pancreatic cancer ♦ Delivering drug to an entire tumor

Nanoparticles at specific temperature stimulate antitumor response Researchers have identified the precise temperature that results in a distinct body-wide antitumor immune response that resists metastatic disease.

Anti-cancer therapy delivering drug to an entire tumor developed To treat inoperable tumors, anti-cancer medicine is commonly used. However, efficient drug delivery to tumor cells is often difficult, treating an entire tumor with drugs even more so. A new anti-cancer nanotechnology has been developed by researchers that delivers anti-cancer drugs uniformly to an entire tumor

Melanoma's 'safe haven' targeted for shut-down Melanoma cells become drug resistant by using surrounding healthy cells to provide a ‘safe haven’ from treatment, according to new research. So even if some cancer cells are destroyed, the protected cancer cells may survive -- and the disease can recur in a form that is untreatable. Now scientists are focusing on these 'safe havens'.

Researchers identify drug target for the first precision cancer therapy Cancerous tumors have the ability to evade targeted therapies by activating alternative pathways. Tumors also contain cancer stem cells, believed responsible for metastasis and drug resistance. Now scientists have identified a drug target that addresses both of these challenges

Identifying patients most at risk of developing pancreatic cancer When people learn they have a lesion in their pancreas that could become pancreatic cancer, they often request frequent CT scans and biopsies, or surgery. Often the lesion is nothing to worry about. A team of international physicians has developed a profile of the patient most at risk of developing lesions that are most likely to develop into cancer

Brain Research:Carbon nanotube fibers make superior links to brain ♦ Research into brain's ability to heal itself ♦ Milk could be good for your brain + more

Research into brain's ability to heal itself offers hope for novel treatment of traumatic brain injury Innovative angles of attack in research that focus on how the human brain protects and repairs itself will help develop treatments for one of the most common, costly, deadly and scientifically frustrating medical conditions worldwide: traumatic brain injury. Continue Reading

Milk could be good for your brain  A correlation between milk consumption and the levels of a naturally-occurring antioxidant called glutathione in the brain has been discovered in older, healthy adults Continue Reading

Brain tumor cells decimated by mitochondrial 'smart bomb'  An experimental drug that attacks brain tumor tissue by crippling the cells' energy source called the mitochondria has passed early tests in animal models and human tissue cultures, say scientists.Continue Reading

Carbon nanotube fibers make superior links to brain  Carbon nanotube fibers may provide the best way to communicate directly with the brain. The research could enable new strategies for treating neurological disorders like Parkinson's Continue Reading

Nanorobotic agents open the blood-brain barrier, offering hope for new brain treatments Magnetic nanoparticles can open the blood-brain barrier and deliver molecules directly to the brain. This barrier runs inside almost all vessels in the brain and protects it from elements circulating in the blood that may be toxic.The research is important as currently 98% of therapeutic molecules are also unable to cross the blood-brain barrier. Continue Reading

Cancer Research: Sweeping prostate cancer review ♦ Tumor sanctuaries ♦ Stress management techniques improve quality of life for women with breast cancer + more

Sweeping prostate cancer review upends widely held view on radiation  Two new studies have upended the widely held view that it's best to delay radiation treatment as long as possible after the removal of the prostate in order to prevent unwanted side effects. The findings inject hard facts into a debate Continue Reading

Cancer therapy 'tumor sanctuaries' and the breeding ground of resistance  Tumors acquiring resistance is one of the major barriers to successful cancer therapy. Scientists use mathematical models to characterize how important aspects of tumor microenvironment can impair the efficacy of targeted cancer therapies. Continue Reading

Stress management techniques improve long-term mood and quality of life for women with breast cancer  A new study shows that providing women with skills to manage stress early in their breast cancer treatment can improve their mood and quality of life .Continue Reading

New potential for personalized treatments in bowel cancer  Genetic changes in bowel tumors are linked to the way the body’s immune system responds to the cancer. Scientists can now start looking at what causes a weak immune Continue Reading

Immune markers discovered that can predict ovarian cancer patients' response to treatment  A biomarker that will help lead to better predictions of the success of chemotherapy in ovarian cancer patients has been discovered by researchers. This discovery could lead to better treatment options in the fight against ovarian cancer  Continue Reading

Novel Approach Gives Insights Into Tumor Development

Lung cancer is the most common cause of cancer deaths both nationwide and worldwide. Past studies have found many genetic alterations involved in lung cancer development. However, tumor growth and metastasis occurs amid complex, evolving, and diverse genetic changes. A major challenge in understanding the cancer genome is to identify the genetic changes that specifically drive the process of tumor development.

An early primary tumor, top, has a diverse pool of mutant cells. As the tumor develops, middle, a limited number of cells dominate. Only a small subset of cells, bottom, cause metastases. Images by the researchers, courtesy of Cell.

To systematically test the effects of mutations across the cancer genome, researchers at the Massachusetts Institute of Technology and their colleagues used a technique called a CRISPR-Cas screen to disrupt specific sequences. Bacteria use the CRISPR-Cas system to protect themselves from invaders. Short stretches of genetic material from bacteriophages (viruses that attack bacteria) and plasmids (pieces of DNA exchanged between bacteria) are incorporated into the system to detect targets for destruction in the future.

For target sequences, the scientists used a pooled genome-wide mouse library of more than 67,000 short genetic sequences called single-guide RNAs, or sgRNAs. The library included more than 20,000 protein-coding genes and almost 1,200 microRNA sequences, which help regulate gene expression and have been implicated in various cancers. Using a cell line derived from a mouse non-small-cell lung cancer, they added the CRISPR-Cas system genes and then the sgRNA library. The work, led by Drs. Feng Zhang and Phillip Sharp, was funded by NIH’s National Cancer Institute (NCI) and others. Results were published on March 12, 2015, in Cell.

When injected under the skin of immunocompromised mice, the collection of mutant cells formed tumors at the injection site that metastasized to the lungs. Late primary tumors contained only a fraction of all the sgRNAs in the collection—less than 4%. Metastases were dominated by a very small number of sgRNAs—on average, only 3.4 per lung. These results suggested that cells with greater ability to proliferate dominated the tumors over time, and that metastases were seeded by a small set of cells.

The team tested a more select pool of sgRNAs from lung metastases in the genome-wide screen. This approach allowed them to quickly test multiple sgRNAs and see how the mutations competed. Mice transplanted with this subpool had a dramatically higher rate of lung metastasis. The metastases retained only a small fraction of sgRNAs, suggesting that these sgRNAs can outcompete others during tumor growth and metastasis.

Mutations in many of the identified genes have been implicated in human cancers. When the team analyzed gene expression in metastatic tumors from patients with non-small-cell lung cancer, most of the genes (up to 75%) were downregulated. Future sequencing of patient metastases may further connect the genes identified in this study to the clinic.

“Tumor evolution is an extremely complex set of processes, or hallmarks, controlled by networks of genes,” Sharp says. Identifying the changes that are important for tumor development could lead to more targeted therapies, better prevention, and new detection strategies.

—by Harrison Wein, Ph.D.

11/16/14 Health News: Nasal spray for migraine relief ♦ Should pregnant & breastfeeding women ♦ Tumor-Attacking Virus ♦ Time spent cooking at home linked to healthier diet

First-in-class nasal spray demonstrates promise for migraine pain relief

Researchers are developing a novel prochlorperazine nasal spray formulation as a potential new treatment for migraines. Of the 100 million people that experience headaches in the United States, 37 million of them suffer from migraines Continue Reading

To eat fish or not to eat fish: Pregnant, breastfeeding women ask the question

To eat fish or not to eat fish? That is the question for pregnant and breastfeeding women. An expert clarifies this complicated issue in a new article. Continue Reading

Tumor-Attacking Virus Strikes With 'One-Two Punch'

Cancer researchers developed a tumor-attacking virus that kills brain-tumor cells and blocks tumor blood-vessel growth. The research shows that viruses designed to kill cancer cells -- oncolytic ..Continue Reading

Time spent preparing meals at home linked to healthier diet Spending less than one hour a day preparing food at home is associated with eating more fast food and spending more money eating out, finds new research. Not having time available may be one of the most significant barriers to achieving a healthy diet. Continue Reading