Triple Lung Cancer Therapy With Experimental Drugs And Radiation Targets Most Resistant Cancers

The four most common gene mutations that occur in lung cancer include KRAS, TP53, STK11, and EGFR, These are often what make those cancers treatment-resistant. As a result, it’s far more difficult to choose the right therapy for lung cancers with genetic mutations.

One new study out of Thomas Jefferson University in Philadelphia, however, has been experimenting with a triple therapy that has proved effective for KRAS gene mutations in mice. The triple therapy involves two experimental drugs in combination with radiation therapy.

“Currently, there is a clinical trial underway to evaluate the combination of two cancer drugs, trametinib and palbociclib, made by two pharma companies for patients with solid tumors and melanoma,” said Dr. Bo Lu, professor of radiation oncology at Thomas Jefferson University and an author of the study, in the press release. “Although further research in human subjects is needed to confirm the finding, our study suggests that we may be able to identify non-small cell lung cancer patients who are likely to benefit most from this combination of therapies.”

Past research has focused on EGFR mutation treatments, but not much has been developed to target the KRAS mutation. Lung cancers, in general, have about a 54 percent survival rate of five years? but only if the cancer is detected early when it’s localized in the lungs. According to the new research, only about 2 percent of lung cancer survivors live past the five-year mark.

For the study, the researchers examined non-small cell lung cancer (NSCLC) cells and applied a KRAS-targeting drug to them. They found that some cells were more resistant to the drug than others and that a certain other mutation called p16 contributed to their resistance. In addition, after reviewing lung-cancer patient genotypes, the authors found that people who had the p16 mutation were less likely to survive, compared to those without the mutation.

This is what helped the researchers decide to use a double drug: The first one targets the KRAS mutation, while the second one unravels the p16 mutation resistance. This would weaken the cancer cells enough to make them fall prey to radiation. Though the treatment proved effective in mice, the researchers will need to repeat the experiment in a clinical trial before moving forward.

“If you hit one target another can take over,” Lu said. “If you hit two, it becomes a lethal bullet.”

Source: Lu B, et al. Clinical Cancer Research, 2015.

By Lecia Bushak / Medical Daily

Biologic Drugs: How They Treat Conditions Like Rheumatoid Arthritis, And How They Stack Up To Synthetics

When we take a trip to the medicine cabinet, chances are most of us are on the hunt for a synthesized, complex compound. Basically, the medications we know and love are mostly made in labs, created through a series of chemical reactions. There are, however, other types of drugs around, even if they’re not as well-known? biologic agents.

These drugs are derived from proteins; and are produced by living organisms like yeast and bacteria, rather than made in a lab. Insulin, for example, is made through a recombinant process and bacteria. Biologic drugs are unfortunately costly to manufacture, but they have a range of skills much different from other, synthetic drugs.

Biologic agents are still used to target disease, but the way it takes action is a bit more complicated than most of its synthesized counterparts. Biologic drugs can replace our body’s proteins (like insulin), disrupt disease processes, or trigger reactions in the body. One example is with conditions like Crohn’s Disease or Rheumatoid arthritis, which cause pain because of inflammation. One way to reduce inflammation is to bind pro-inflammatory cytokines with biologic drugs, keeping the inflammatory cytokines from binding to the cells of the body.

Check out the video to learn more about biologic drugs, including a comparison of these drugs to their synthetic counterparts; and a deeper explanation of expenses.

Ali Venosa / Medical Daily

Medical Miracle Or Playing God: Human Chimeras Made With Man, Animal Cells Provide New Hope For Organ Transplants

In a world where the demand for organ transplants greatly outnumbers the availability of organ donors, a small division of scientists believes they have a solution: growing human organs inside the bodies of farm animals. Despite the National Institutes of Health (NIH) recently denouncing such projects, some independent U.S. research centers have decided to go ahead with plans to grow humans tissue and organs inside the bodies of genetically altered pigs and sheep.

The complicated process would produce something known as a chimera: an organism with an extra set of DNA that it didn’t inherit from either of its parents. Though they sound like something out of a science-fiction novel, they’re actually a common natural occurrence? they can result from blood transfusions, organ transplants, or in-vitro DNA exchanges between mothers their fetuses. Sometimes they even result from the absorption of one twin in the womb by the other.

With regard to an animal-human chimera, it would be produced from a combination of stem cell technology and gene-editing. Though controversial, the procedure is technically feasible. In a presentation at the NIH’s Maryland campus last November, Dr. Juan Carlos Izpis?a Belmonte of the Salk Institute showed unpublished data from more than a dozen pig embryos that contained human cells. Based on interviews with three U.S. based research teams, the MIT Technology Review estimates about 20 pregnancies involving pig-human or sheep-human chimeras have occurred in the past year. However, none of these animals have gestated to full-term.

In order to create such a creature, scientists must first tweak the DNA inside sheep and pig cells using gene-editing technology, so that the developing embryo will lack certain organs, IFL Science reported. “We can make an animal without a heart,” said Dr. Daniel Garry, a cardiologist who leads a chimera project at the University of Minnesota, according to the MIT Technology Review. “We have engineered pigs that lack skeletal muscles and blood vessels.”

Under normal circumstances, these embryos would not survive without such important organs. But scientists have developed a way to replace the missing cells with stem cells from another species’ embryo in order to grow the missing organ. In 2010, for example, Japanese scientists successfully created mice with pancreases made entirely of rat cells. Breeding sheep and pigs with salvageable human organs would be completely new territory, however.

Though most scientists believe it’s possible, some believe the endeavor poses serious ethical concerns, arguing that it’s unclear if the animal’s human qualities will extend past their organs. “What if the embryo that develops is mostly human?” Pablo Ross, a veterinarian and developmental biologist at the University of California, Davis, told the MIT Tech Review while adding this wasn’t something that he could rule out.

“The specter of an intelligent mouse stuck in a laboratory somewhere screaming ‘I want to get out’ would be very troubling to people,” NIH ethicist David Resnik added during the NIH meeting. Still, the chances of either of these results occurring are unlikely, since only about 0.5 percent of animal-human chimeras’ cells are human.

This past fall, the NIH, one of the world’s foremost medical research centers, announced that it will not fund any study involving human-animal chimeras unless more evidence is presented. But even without NIH funding, the demand for more viable organs for transplant operations, and the sheer curiosity surrounding such a taboo subject, could make human-animal chimeras a reality sooner than you think.

Dana Dovey / Medical Daily

New Blood Test Is 99.6% Accurate, Safely Identifies Patients At Low Risk Of Heart Attack

A simple blood test can accurately identify patients at very low risk for heart attack, say, researchers. Almost two-thirds of people who arrive in an emergency room complaining of chest pain and fearing cardiac arrest might be safely discharged, the results of the new study suggest.

“Implementation of this approach would reduce avoidable hospital admission and have major benefits for both patients and health-care providers,” wrote the authors sponsored by the University of Edinburgh and funded in part by the British Heart Foundation.

When patients complain of chest pain, doctors make a diagnosis of myocardial infarction (heart attack) based on evidence of heart muscle damage. Specifically, they use a blood test that measures a protein (or chemical) known as troponin, which is released into the blood by damaged heart muscles. A high troponin level or even slight elevation can indicate injury to the heart, according to the American Association for Clinical Chemistry.

When levels of troponin are unusually high or if a series of tests performed over several hours show elevated levels, doctors take this as proof that a patient has had a heart attack or some other cardiac event.

Commonly, emergency room doctors perform the test on someone complaining of chest pain when they are first admitted and then again 12 hours later.

Recently, a more sensitive troponin test, which is capable of measuring finer levels of troponin, was introduced. Importantly, the new test needs to be performed only once. The new study, then, investigated whether the more sensitive test might more accurately diagnose and predict a heart attack.

Conducting the research at hospitals in Scotland and the United States, the science team measured blood troponin concentrations using the high-sensitivity test for 6,304 patients with suspected heart attacks.

“Low plasma troponin concentrations identify two-thirds of patients at very low risk of cardiac events who could be discharged from the hospital,” wrote the researchers, who say the high sensitivity test was 99.6 percent accurate.

Symptoms of a heart attack include chest discomfort or pain (that often feels like squeezing), upper body pain, stomach pain, shortness of breath, anxiety, lightheadedness, sweating, and nausea and vomiting. According to the American Heart Association, women most commonly experience chest pain or discomfort just like men, but they are more likely than men to experience other symptoms, particularly shortness of breath, nausea/vomiting, and back or jaw pain.

Source: Shah ASV, Anand A, Sandoval Y, et al. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. The Lancet. 2015.

Susan Scutti / Medical Daily

A ‘Grenade’ For Killing Cancer Uses Heat To Target Cells, Release Cancer-Fighting Drugs

Normally, grenades are bad for your health. They explode, spreading shrapnel and other incendiaries into a thousand different directions, with only one purpose: causing maximum harm to anyone unlucky enough to be within the blasts’ radius. Fortunately, the grenade we’re talking about today does more good than bad, as it targets and kills cancer tumors.

Researchers from the University of Manchester will present two studies at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool that describes cancer drug-packed “grenades” with heat-sensitive triggers that allow for the direct treatment of cancerous tumors. The “grenades” are actually liposomes? small, bubble-like structures built out of cell membrane? and they’re used as packages to deliver drugs into the cancer cells. The challenge the researchers faced was being able to target tumors with the cancer drug-carrying liposomes, while also keeping healthy tissue intact.

The two studies show how the team managed to clear this hurdle by giving the liposomes heat-activated triggers. Testing the liposomes in a cell culture and lab mice, the team found that by slightly heating the tumors with warm water baths and heating pads, it was able to pinpoint the exact place where cancer resided? the “grenades” could then detonate and release the drugs.

“Temperature-sensitive liposomes have the potential to travel safely around the body while carrying your cancer drug of choice,” said Kostas Kostarelos, study author and professor of nanomedicine at the University of Manchester, in a press release. “Once they reach a ‘hotspot’ of warmed-up cancer cells, the pin is effectively pulled and the drugs are released. This allows us to more effectively transport drugs to tumors, and should reduce collateral damage to healthy cells.”

The researchers set the thermal triggers of the liposomes to 42 degrees Celsius (107 degrees Fahrenheit), which is slightly higher than normal body temperature. But, according to Kostarelos, “this work has only been done in the lab so far; [however], there are a number of ways we could potentially heat cancer cells in patients? depending on the tumor type? some of which are already in clinical use.”

These studies open up a “range of new treatment avenues,” said Professor Charles Swanton, chair of the 2015 NCRI Cancer Conference, in the press release. “This is still early work, but these liposomes could be an effective way of targeting treatment toward cancer cells while leaving healthy cells unharmed.”

Source: Kostarelos K, et al. National Cancer Research Institute Cancer Conference. 2015.

By Steve Smith / Medical Daily