Category Archives: Transhuman News

MONDAY, June 5, 2017 (HealthDay News) -- Two drugs that target genetic flaws are giving people with specific types of advanced lung cancer a chance to live longer and better, a pair of new clinical trials finds.

A newly approved drug called alectinib (Alecensa) works twice as long as the current standard medication in halting cancer growth in patients with ALK-positive non-small cell lung cancer, results from a new global clinical trial show.

ALK is a gene that produces a protein that helps cancer cells grow and spread, according to the American Cancer Society (ACS).

In another study, an experimental drug called dacomitinib delayed cancer growth by about half in non-small cell lung cancer patients who had a mutation of the epidermal growth factor receptor (EGFR) that caused cancer cells to grow faster, a second trial reported. Non-small cell lung cancers comprise most lung cancer cases.

EGFR is a substance normally found on cells that helps them grow and divide, the ACS says.

The drugs, alectinib in particular, will let people live months or years longer just by taking a daily pill, said Dr. Bruce Johnson, chief clinical research officer at Dana-Farber Cancer Institute in Boston. Johnson is also incoming president of the American Society of Clinical Oncology (ASCO).

Alectinib works more than a year longer than crizotinib (Xalkori), which itself supplanted chemotherapy a few years back because it proved more effective with fewer side effects, Johnson said.

"This is kind of a game changer, because the drug itself works at least for two years, plus there are other treatments" that can be substituted when it ultimately becomes ineffective, Johnson said of alectinib. "We used to have to tell these patients 10 or 15 years ago that you've got eight months to a year. Now they most likely have years."

Both of these genetically driven forms of lung cancer are more common in nonsmokers, the ACS says.

The studies were both funded by the drug manufacturers. Hoffmann-La Roche funded the alectinib study. Pfizer and SFJ Pharmaceuticals Group funded the dacomitinib study.

The first clinical trial revealed that alectinib halts lung cancer growth for about 26 months on average. That compared to about 10 months on average for crizotinib, the drug now used as front-line treatment for ALK-positive patients.

Alectinib also works 84 percent better than crizotinib at preventing spread of advanced lung cancer to the brain, because it is better able to penetrate into the brain and kill cancer cells there, said lead researcher Dr. Alice Shaw, director of thoracic oncology at Massachusetts General Hospital Cancer Center in Boston.

About 5 percent of non-small cell lung cancer cases are ALK-positive. That means they have a genetically abnormal protein that fuels cancer growth. In the United States, about 12,500 people are diagnosed with ALK-positive non-small cell lung cancer each year, researchers said in background information.

Alectinib already is approved in the United States as a treatment for ALK-positive patients who no longer respond to crizotinib, Shaw said.

The results should "establish alectinib as the new standard of care" for ALK-positive lung cancer patients, rather than crizotinib, Shaw said.

ASCO expert Dr. John Heymach agreed, calling the clinical trial a "watershed moment."

Not only did the drug work better and longer, but it also produced fewer side effects in patients, noted Heymach, chair of thoracic/head and neck oncology for the University of Texas MD Anderson Cancer Center in Houston.

The most common side effects for alectinib were fatigue, constipation, muscle aches and swelling, while crizotinib patients most often suffered from gastrointestinal problems and liver enzyme abnormalities, according to the researchers.

The second clinical trial compared a new drug, dacomitinib, to the current standard targeted drug gefitinib (Iressa) in treating EGFR-positive lung cancer.

Each year about 15,000 people in the United States are diagnosed with EGFR-positive lung cancer, which involve mutations that increase the growth of cancer cells, researchers said in background notes.

Dacomitinib blocked EGFR mutations more effectively than first-generation drug gefitinib, providing a 41 percent lower chance of cancer progression or death, researchers found. On average, dacomitinib halted cancer growth for 14.7 months in patients, compared with 9.2 months with gefitinib.

"From the perspective of doctors who treat lung cancer daily, this is really a substantial advance," Heymach said, noting that the results put the drug "at the front of the pack in terms of efficacy."

However, dacomitinib also created more side effects, including acne in about 14 percent of patients and diarrhea in 8 percent of patients. Doctors wound up reducing the dosage in about 66 percent of patients as a result of side effects, said lead researcher Dr. Tony Mok, chair of clinical oncology at the Chinese University of Hong Kong.

Heymach said the side effects are "not life-threatening toxicities."

"These are toxicities that doctors who treat this for a living become accustomed to managing," Heymach said.

"At the end of the day, I think we now have one additional choice" in treating EGRF-positive non-small cell lung cancer, Mok concluded, adding that dacomitinib should be considered as a new first-line alternative treatment. The drug has not received FDA approval.

Neither of the tested drugs will be cheap. "Almost all these targeted drugs are thousands of dollars per month," Johnson said.

The results of both trials were scheduled to be presented Monday at ASCO's annual meeting, in Chicago. The findings were also being published June 6 in the New England Journal of Medicine.

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Gene-Targeted Drugs Fight Advanced Lung Cancers - Sioux City Journal

SATURDAY, June 3, 2017 (HealthDay News) -- An experimental drug that targets a specific gene mutation can battle a range of advanced cancers in adults and children, researchers are reporting.

The genetic abnormality is known as a TRK fusion, and it's found in only a small percentage of all cancers. So the drug, called larotrectinib, is no panacea.

But researchers found that among 50 patients with TRK fusions, 76 percent saw their cancer regress after starting larotrectinib -- regardless of their age or type of cancer.

For most of those patients -- 79 percent -- the response has lasted at least one year, according to lead researcher Dr. David Hyman.

"There are few therapies that have had that kind of success for patients like these," said Hyman, an oncologist at Memorial Sloan Kettering Cancer Center in New York City.

Dr. William Oh, an oncologist who was not involved in the study, agreed.

"A 76 percent response rate for a new drug is extremely exciting," said Oh, chief of hematology and medical oncology at the Icahn School of Medicine at Mount Sinai in New York City.

"More importantly," he added, "the responses have been durable, lasting over a year -- which for some of these aggressive cancers is very promising."

This is the latest drug to target flaws in genes that occur anywhere in the body instead of just going after an organ-specific tumor. The first drug to work this way -- Keytruda (pembrolizumab) -- was approved for targeted use by the U.S. Food and Drug Administration on May 24. (Keytruda had previously received traditional FDA-approval for some organ-specific cancers.)

Targeted therapies are designed to zero in on specific abnormalities found on tumor cells -- with the aim of killing off the cancer while sparing healthy cells.

The patients in Hyman's study had a range of cancers, including colon, lung, pancreatic and gastrointestinal tumors -- as well as melanoma skin cancer and sarcoma, which arise in the bones or soft tissue like muscle or body fat.

But they also had some things in common: Their cancer had spread beyond its original tissue, sometimes to distant sites in the body. And they all had tumors marked by TRK fusions.

The abnormality is a "rare event," Hyman said.

TRK fusions occur in only about 0.5 percent to 1 percent of common cancers, such as colon, breast and lung cancers. But Hyman said they are very common in certain rare cancers such as salivary gland cancer, a form of breast cancer that affects children, and a type of sarcoma in babies.

The abnormality arises when a TRK gene in a cancer cell joins with one of many potential "partner" genes. (Scientists have found more than 50 so far). That, Hyman explained, results in TRK fusion proteins that are constantly "turned on," signaling the cancer cells to keep growing and dividing.

Larotrectinib, an oral medication, is designed to block that TRK activity wherever it occurs.

The new study involved 55 patients, including 12 children. So far, 50 have been on the drug long enough to track their progress.

Overall, Hyman said, about three-quarters have responded to treatment -- meaning their cancer regressed by at least 30 percent. Of those patients, eight in 10 were still on the drug and responding at the one-year mark.

At this point, Hyman said, the longest treatment response has been 25 months and counting.

The most common side effects are fatigue and dizziness. "Patients do very well on it," Hyman said. "You can have a good quality of life while you're taking it."

Last year, the FDA granted larotrectinib "breakthrough therapy" status. That helps speed the development and review process of promising new treatments for serious diseases.

Hyman said he couldn't estimate how long an FDA approval could take.

If the drug is approved, then the question will be: Who should get tested for TRK fusions?

According to Hyman, patients with advanced-stage cancer would have the "greatest need." And even though TRK fusions are uncommon, he thinks testing would be appropriate regardless of the cancer type.

Oh agreed. "TRK fusions are very rare, but in those patients who have them, the consequences with this drug appear to be very significant."

Plus, Oh said, cancer patients are already being tested for other molecular abnormalities to see if they can benefit from targeted drugs. That testing is becoming technically easier and cheaper, he noted.

Dr. Sumanta Kumar Pal is a medical oncologist at City of Hope in Duarte, Calif., and chair of ASCO's Cancer Communications Committee.

He said larotrectinib has the chance to be a "bit of game-changer. There are two important points: This drug may be active irrespective of the cancer site, and irrespective of age."

And while the safety results were encouraging, "it's difficult to draw conclusions based on such a small group of patients," he added.

If the drug is approved by the FDA, Pal said it would make sense to "test early" for TRK fusions in patients with the rare cancers. But with many common cancers, "we'd probably stick with standard care, and then (test) only if that fails," he said.

The study was funded by Loxo Oncology, Inc., which is developing larotrectinib. Hyman and some of his colleagues have received funding from or served as consultants to the company.

Hyman was scheduled to present the findings Saturday at the American Society of Clinical Oncology's annual meeting, in Chicago. Study results presented at meetings are usually considered preliminary until they're published in a peer-reviewed medical journal.

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Experimental Gene-Targeted Drug Hits Cancer Where It Lives - Montana Standard

Picture a time in the not-too-distant future when whole genome sequencing is routine. A time when, before babies even learn to talk, their parents will have the ability to learn what the future may have in store for their offspring: Is their little girl predisposed to getting breast cancer? Will their happy-go-lucky son one day develop Alzheimer's?

"There is no doubt in my mind that, in addition to going in and having blood chemistry done, you're gonna have DNA sequencing done, too. It will be there at some point," says Nicholas Schork, a quantitative geneticist at the J. Craig Venter Institute in La Jolla, California, who has studied genomic medicine for more than three decades. "We can debate about the timeline, but it'll become routine."

The hope is that genetic testing will make health care more effective by allowing doctors and patients to focus on areas that need attention the patient's genetic "vulnerabilities." At the same time, patients may learn of areas where they won't need to be quite as vigilant. And treatments could, in turn, be perfectly tailored to a patient's specific needs.

But as with any significant and broadly applicable medical advance, there are questions. For example, should patients learn that they carry markers for currently incurable genetic diseases, or that they are at high risk for developing a condition like Alzheimer's, which has no effective treatment? And just who owns all that genetic data? Who will have access to it?

Even with important questions left unanswered, health educators are moving forward to take advantage of the promises genetic testing offers. Washington State University's new Elson S. Floyd College of Medicine has announced it is partnering with Arivale, a Seattle-based company that conducts whole genome sequencing, to help complete a portrait of a person a "portrait" that can be used to promote wellness over that individual's entire lifespan. Every member of the school's inaugural class will have the opportunity to undergo testing, which will also include blood tests and a lifestyle evaluation. Then, over the next year, Arivale's team of nurses and dietitians will provide individually tailored follow-up, based on each individual's risks and goals. It's a unique partnership, made possible in large part because the medical school is new, with its first class of students starting in 2017.

Allowing the medical students to experience genetic testing firsthand is just part of the goal. "We need physicians that understand it well enough that they can make it better going forward," says John Tomkowiak, founding dean of WSU's College of Medicine. "That's where our students are going to be uniquely positioned."

WHAT GENES TELL US

Genetic testing already provides important information about a person's health or their heritage. Hospitals screen newborn babies for certain genetic disorders, and in some cases, tests can detect disorders before birth. And diagnostic testing can confirm, or rule out, many disorders in adults.

Testing doesn't have to be ordered by a physician. For $200, you can provide a saliva sample, mail it back to 23andMe.com and find out not only your ancestry, but also your risks for a number of diseases, including Alzheimer's and Parkinson's. Ancestry.com offers a glimpse into your heritage for $99. Color.com claims to reveal your risk for the most common hereditary cancers, and even offers "complimentary genetic counseling" for a $249 fee.

But if genetic testing is to revolutionize the health care industry, as many have promised, there's still a ways to go. "The technology is at the beginning stages," says Thomas May, a faculty researcher for the HudsonAlpha Institute for Biotechnology.

Companies like 23andMe offer genetic tests that may provide information about some genetic disorders from currently known genetic variants. But whole genome sequencing is different; it will reveal all your individual genetic variants.

How valuable is that information? There are a relatively small number of conditions that researchers are confident result from a specific genetic variant, May says. For example, there is one variant that researchers have found is associated with an increased risk of developing breast or ovarian cancer. A genetic test that shows an increased risk for breast cancer is considered an "actionable" outcome, meaning there are things you can do to prevent the outcome, like beginning mammograms earlier. Though there are more than 50 actionable outcomes like that, it's still a relatively small number.

Adding to the confusion is the fact that not everyone who develops breast cancer actually has the genetic variant in fact, May says only about 10 percent do. So even if testing shows that you don't have the "breast cancer gene," that doesn't mean it's OK to stop getting mammograms.

"Most variants and correlations are of that type: We can't say for certain if you're gonna get a disease," May says.

Doctors are mixed about whether genetic testing is currently having a real impact on patients. In a May survey conducted by the Medscape Physician Oncology Report on Genomics Testing, 71 percent of oncologists surveyed felt that genetic testing was either "very" or "extremely" important to the oncology field. At the same time, 61 percent said that, currently, fewer than a quarter of their patients would actually benefit from genetic testing.

The number of diseases with "actionable" outcomes will inevitably grow, as more people are tested and more data becomes available. But this leaves deeper questions, says Schork, the quantitative geneticist. A company or health care provider would likely give patients information about diseases that can be prevented or cured. If someone is predisposed to obesity, for instance, then he or she can elect to receive targeted care to reduce that risk.

But what about diseases that, right now, are incurable?

Take Huntington's disease, a genetic disorder that breaks down nerve cells in the brain. It's rare, but it's a "hideous way to die," Schork says. A person can be screened at the age of 25 and be found to carry the Huntington's gene, but there's debate about whether or not that information should be shared with a client or not. The same goes for genetic variants related to Alzheimer's disease.

"If there's nothing they can do about it, then there's a concern about whether or not that information should be imparted," Schork says.

When the Food and Drug Administration ordered 23andMe to stop telling customers their odds of contracting diseases in 2013, Harvard Medical School genetics professor Robert Green and Laura Beskow, a professor at Duke University's Institute for Genome Sciences and Policy, argued against the FDA. They cited a number of studies showing that direct-to-consumer genetic testing does not cause a large percentage of customers despair. In an interview with the New York Times in April, Green said the potential for distress based on results of a genetic test for Alzheimer's was "much smaller than anticipated."

Another question: Who really owns the DNA data that is being collected from willing users of genetic testing? Consider Myriad, a company that offers genetic testing both to help determine cancer risk and design better treatment plans for patients who already have cancer. The company has something that "others do not," Schork says: insight into which genetic variants predispose women to breast cancer.

What Myriad is really selling, then, is not the genetic test itself, but access to insights it has gained through mining its database, insights that can be leveraged into whatever level of payment the company decides to charge.

It's potentially critical information that could help save a life, and some argue that the data should be in the public domain not held by a private company.

"There have been huge debates about whether the community should challenge the monopoly that Myriad has," Schork says. "There are many groups out there that would like to counteract the monopoly Myriad has, by building public domain data sets."

JUST ONE TOOL

"Genetic testing is not a blueprint. It's really not," says Jennifer Lovejoy, chief translational science officer for Arivale. "Genes are really just one factor the environment, diet, exercise, pollutants and even emotional state have a big impact on genes."

That's why Arivale not only collects genetic information on each client, but also evaluates various blood tests and lifestyle factors to create a "dense data cloud" of information about a patient.

"That is the grand vision: that everybody would have these dense, dynamic data clouds, and understand the choices that will be optimal to optimize wellness and avoid disease," says Lovejoy.

Arivale touts the success stories among its nearly 2,000 clients. One client found out he had a gene associated with high sensitivity to saturated fat, giving him a better indication of an appropriate diet that helped him lose weight. Another client discovered that his genes may have an impact on his cholesterol. Another learned he was at risk of developing diabetes.

Ideally, this type of preventive care will soon be covered by insurance, Lovejoy says. The thinking is that preventing disease will bring down the cost of health care overall, making insurers likely to cover more preventive care, "but we have to prove it," Lovejoy says. Researchers are conducting studies and trials to do just that, and if they can prove it, then genetic testing could soon be routine in health care.

"If you think about what health care should mean, it should mean, one, the ability to deal with disease and that's what everyone does today," Arivale co-founder Leroy Hood said at a press conference in April announcing the company's partnership with WSU. "But two, it should mean the ability to optimize wellness for each individual. That is, improving their health and/or letting them avoid disease." That's a concept Hood calls "scientific wellness, and he thinks it could lead to "a whole new health care industry in the future."

Tomkowiak, of WSU's College of Medicine, agrees: "The concept of scientific wellness has the potential to disrupt the entire industry by shifting the cost curve, by keeping people healthier and reducing the cost of health care overall."

Regardless of whether or not Arivale becomes an industry leader, Tomkowiak believes that the practice of medicine will be fundamentally altered in the near future.

"We absolutely believe that seven years from now, the practice of scientific medicine and scientific wellness will be common," he says. "Instead of being behind the curve, we want... to be leading this effort."

For about $3,500, clients can sign up for Arivale's program. The fee includes whole genome sequencing, which is also available from other sources. So how do Arivale clients achieve "scientific wellness"? Here are the elements of their program:

Welcome package: Clients get a welcome package with a Fitbit to track sleep, activity and heart rate. The package asks for information to help understand a client's bacteria in their gut, and asks for a sample of saliva to measure a person's stress level.

Online test: Clients take a series of online assessments about their goals, health history, lifestyle, stress, personality and happiness.

Call from coach: You'll talk to a coach who will get to know what you want to accomplish and give you a personalized action plan.

Labs: You'll take blood tests so your coach can understand your current health. While you're there, they'll take your vital signs.

A picture emerges: The various test create a picture of you, which an Arivale coach will use to provide a step-by-step plan to "optimize your wellness," according to the company.

Follow-up: You're not done yet. You'll be contacted by your coach regularly to review your action plan, and Arivale will provide reports on how you're progressing. Every six months, you'll complete another set of clinical labs.

Source: arivale.com/your-journey

Continued here:
What's In Your Genes? - Pacific Northwest Inlander

MONDAY, June 5, 2017 (HealthDay News) -- Genetically tuning a person's own immune cells to target cancer appears to provide long-lasting protection against a blood cancer called multiple myeloma, an early trial from China shows.

The treatment, called CAR T-cell therapy, caused 33 out of 35 patients with recurring multiple myeloma to either enter full remission or experience a significant reduction in their cancer.

The results are "impressive," said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

"These are patients who have had prior treatment and had their disease return, and 100 percent of the patients are reported to have had some form of meaningful response to these cells that were administered," Lichtenfeld said.

The new therapy is custom-made for each patient. Doctors collect the patient's own T-cells -- one of the immune system's main cell types -- and genetically reprogram them to target and attack abnormal multiple myeloma cells.

Lead researcher Dr. Wanhong Zhao likened the process to fitting immune cells with a GPS that steers them to cancer cells -- making them into professional killers that never miss their target.

Zhao is associate director of hematology at the Second Affiliated Hospital of Xi'an Jiaotong University in Xi'an, China.

CAR T-cell therapy is promising because the genetically altered T-cells are expected to roost in a person's body, multiplying and providing long-term protection, Lichtenfeld said.

"The theory is they should attack the tumor and continue to grow to become a long-term monitoring and treatment system," Lichtenfeld said. "It's not a one-shot deal."

The technology represents the next step forward in immunotherapy for cancer, said Dr. Michael Sabel, chief of surgical oncology at the University of Michigan.

"Immunotherapy is now really providing hope to a lot of patients with cancers that were not really responding to our standard chemotherapies," Sabel said.

CAR T-cell therapy previously has been used to treat lymphoma and lymphocytic leukemia, Lichtenfeld said.

Zhao and his colleagues decided to try the therapy to treat multiple myeloma. They re-engineered the patients' T-cells and then reintroduced them to the body in three infusions performed within one week.

Multiple myeloma is a cancer that occurs in plasma cells, which are mainly found in bone marrow and produce antibodies to fight infections. About 30,300 people will likely be diagnosed with multiple myeloma this year in the United States, researchers said in background notes.

"Multiple myeloma is a disease that historically was fatal in the course of a couple of years," Lichtenfeld said. During the past two decades, new breakthroughs have extended survival out 10 to 15 years in some patients, he noted.

To date, 19 of the first 35 Chinese patients have been followed for more than four months, researchers report.

Fourteen of those 19 patients have reached the highest level of remission, researchers report. There hasn't been a relapse among any of these patients, including five followed for more than a year.

"That's as far as you can go in terms of driving down the amount of tumor that's in the body," Lichtenfeld said.

Out of the remaining five patients, one experienced a partial response and four a very good response, researchers said.

However, about 85 percent of the patients experienced cytokine release syndrome (CRS), a potentially dangerous side effect of CAR T-cell therapy.

Symptoms of cytokine release syndrome can include fever, low blood pressure, difficulty breathing, and impaired organ function, the researchers said. However, most of the patients experienced only transient symptoms, and "now we have drugs to treat it," Lichtenfeld said.

History suggests the therapy will cost a lot if it receives approval, Lichtenfeld said. However, prior to approval, much more research will be needed, he added.

The Chinese research team plans to enroll a total of 100 patients in this clinical trial at four hospitals in China. They also plan a similar clinical trial in the United States by 2018, Zhao said.

The study was funded by Nanjing Legend Biotech Co., the Chinese firm developing the technology.

The findings were presented Monday at the American Society of Clinical Oncology annual meeting, in Chicago. Data and conclusions presented at meetings are usually considered preliminary until published in a peer-reviewed medical journal.

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Gene-Based Therapy May Thwart a Tough Blood Cancer - Montana Standard