Onco Actu du 28 juillet 2017

	1. Biologie
First draft of a genome-wide cancer ‘dependency map’ [Harvard Gazette] Many of these “dependencies,” the researchers report today in the journal Cell, are specific to certain cancer types. However, about 10 percent of them are common across multiple cancers, suggesting that a relatively small number of therapies targeting these core dependencies might each hold promise for combating several tumors.
Systematically exposing vulnerabilities of cancer cells [Novartis] Novartis team shares results of a massive oncology experiment with the world to accelerate drug discovery.
Enhancers Drive Pancreatic Cancer Metastasis: Study [The Scientist] Mouse organoids reveal that a protein active during embryonic development joins forces with gene enhancers to revert cancer cells to an earlier developmental state.
	3.1.1 Tabac - e-cigs
Study links rising U.S. e-cigarette use to rise in smokers quitting [Reuters] In a study published in the BMJ British medical journal, scientists from California said their findings were based on the largest representative sample of e-cigarette users to date and provided a "strong case" that e-cigarettes have helped to increase rates of smoking cessation.
	3.5 Prévention - UV
Tans — even from a new drug — aren’t the way to prevent skin cancer [STAT] Researchers have a long way to go before a tanning drug hits the market. In the meantime, it’s important to keep in mind the escalating skin cancer epidemic, the dangers of tanning, and the fact that all skin colors are beautiful.
	4. Dépistage, diagnostic et pronostic
Differences in Subtypes of Gastric Cancer May Determine Prognosis and Response to Treatment [AACR] In order to identify the clinical significance of the four subtypes, Lee and colleagues re-analyzed gene expression data for these subtypes using data from the gastric cancer cohort of the TCGA project.
	5. Traitements
Tumors caused by pluripotent stem cells can be tackled with radiation, say Stanford researchers [Stanford Medicine] Now cardiologists Joseph Wu, MD, PhD, Patricia Nguyen, MD, and medical student Andrew Lee, PhD, have found that, at least in mice, it’s possible to halt or reverse the growth of human teratoma cells arising from the injection of pluripotent stem cells with radiation. This is a surprise because naturally occurring teratomas are relatively resistant to the treatment.
Stem cell treatment kills cancer cells that have spread in mice [Cancer Research UK] The study by scientists at the University of California used stem cells that are usually found in bone marrow, but which travel to the site of cancers that have spread.
New strategy against childhood cancer [Karolinska Institutet] In studies on cells in vitro and in mice, the researchers also saw that inhibiting the ROCK enzyme caused the MYCN oncogene, which is linked to the incidence of neuroblastoma, to be degraded to a greater extent and disappear.
	5.10 Traitements - Essais
Tagrisso significantly improves progression-free survival in the Phase III FLAURA trial for lung cancer [AstraZeneca] Tagrisso met the primary endpoint, demonstrating a statistically-significant and clinically-meaningful progression-free survival benefit in 1st-line EGFRm non-small cell lung cancer compared to current standard-of-care treatment.
	5.12.3 Immunothérapies-combinaisons
Why I Don’t Favor an Front-Loaded Approach for Most Advanced NSCLC Patients [Cancer Grace] Importantly, when we talk about the arm of patients getting chemo combined with immunotherapy, we aren’t talking about improving survival. Instead, we’re talking about prolonging the time before patients showed significant progression of their cancer on scans, which leads us to switch to a new treatment.
	5.12.4 Immunothérapies - Essais
Immunotherapy Shakeup: AstraZeneca Inks Merck Deal as Drug Combo Fails [Xconomy] AstraZeneca is a latecomer in cancer immunotherapy, which has begun to change the way multiple cancers are treated. It just won approval of durvalumab in bladder cancer in May, well after rival immunotherapy drugs from Bristol-Myers (nivolumab (Opdivo)), Merck (pembrolizumab (Keytruda)), and others hit the market.
AstraZeneca Gets the Bad News [In the Pipeline] Immuno-oncology is a tremendously exciting field. But we don’t truly understand it, and won’t for some time, and that means that things like this are going to happen. It’ll happen again, too, to someone. Strap in.
AstraZeneca's Mystic shortfall is an immuno-oncology shake-up for Bristol-Myers and a bolster for Merck and Roche [Fierce Pharma] The gist of Mystic’s results so far is this: Imfinzi plus tremelimumab failed to stave off lung cancer progression better than chemotherapy or Imfinzi alone.
AstraZeneca lung cancer immunotherapy trial failure sends shares plunging [STAT] AstraZeneca will continue to follow patients in the MYSTIC study, hoping that the combination of Imfinzi and tremelimumab might help patients live longer than chemotherapy alone. Those overall survival results are expected in the first half of next year.
AstraZeneca's Missing Takeover Defense [Bloomberg] Blame can't be leveled solely at Chief Executive Officer Pascal Soriot. Any science company needs an appetite for risk, just as much as the willingness to pull projects that look unlikely to pay off.
AstraZeneca lung cancer failure sparks 16 percent share fall [Reuters] The so-called MYSTIC study was the most anticipated clinical experiment in the pharmaceutical industry this year and the news saw the shares tumble 16 percent, wiping some $14 billion off the company's value in their biggest ever daily fall.
AstraZeneca’s Cancer Drug Trial Disappoints, Sending Shares Lower [NY Times] The treatment for lung cancer had been expected to be a major driver of growth for AstraZeneca.
AstraZeneca inks $8.4B pact with Merck as crucial MYSTIC study fails and shares plunge [EndPoints] A success here could have vaulted AstraZeneca into the front ranks of a furious assault on a multibillion-dollar market; failure was deemed a disaster.
AstraZeneca reports initial results from the ongoing MYSTIC trial in Stage IV lung cancer [AstraZeneca] Imfinzi plus tremelimumab combination did not meet a primary endpoint of progression-free survival compared to chemotherapy.
	5.12.5 Immunothérapies - Pharma
Cancer drug war heats up as Big Pharma squares off against Genentech [San Francisco Business Times] In its suit, BMS says Genentech's cancer fighting drug Tecentriq, or atezolizumab, is "exploiting" patents for the New York-based company's Opdivo, or nivolumab.
The Keytruda Story [In the Pipeline] Was Merck good, or were they lucky? They were both. And good for them.
Bristol-Myers shares slump after failed AstraZeneca drug trial [Reuters] Bristol-Myers said the Mystic trials and its own CheckMate-227 trials had different designs, drugs, dosing and scheduling. "It’s difficult to make direct comparisons or draw conclusions from one trial to another," spokeswoman Audrey Abernathy said in a statement.
The Startling History Behind Merck's New Cancer Blockbuster [Forbes] The success of pembro was anything but inevitable. It was discovered accidentally, by biotech scientists looking for drugs that would tamp down the immune response in patients with autoimmune disease, and would stimulate, not block PD1.
	5.2 Pharma
Astellas Announces Wind-Down of Agensys Research Operations [Astellas] The field of oncology is ever evolving, and Astellas believes that its research focus also needs to evolve in order to continue to be successful in developing potential therapies to help patients.
Astellas winds down Agensys, turning its back on antibody-drug conjugate research [Fierce Biotech] Astellas paid $387 million upfront for Agensys in 2007, with another $150 million in the offing from milestone payments, buying into the company's expertise in both naked antibodies and ADCs.
Astellas is shuttering Agensys, axing 220 jobs and moving away from ADC tech [EndPoints] The team has provided post-Proof of Concept compounds and antibody-related technology that have been incorporated into our promising oncology pipeline. Yet, the field of research has evolved and led to a new frontier of treatment options.
	5.2.1 Pharma - Partenariats
Tesaro Cashes In Again on PARP Blocker With $100M Takeda Deal [Xconomy] Takeda is paying Waltham, MA-based Tesaro $100 million up front for the rights to niraparib in Japan for all cancer types. Takeda also receives rights to the drug for all tumor types, except prostate cancer, in South Korea, Taiwan, Russia, and Australia.
	5.2.2 Pharma - Fusions & Acquisitions
As drug prices drop, generics makers fight back with deals [Reuters] Generic drug makers are turning to M&A to shield themselves against a concerted effort by U.S. regulators to crack down on steep drug prices.
	5.3 Traitements - FDA, EMA, NICE...
Don’t limit the powers of the FDA [Boston Globe] In other words, the nation’s oldest consumer protection agency, forged in the wake of tragedies, for the explicit purpose of protecting patients, would be blinded to harms linked to the products it would be charged with reviewing for use in the general population.
US, EU filings for Eisai’s lenvatinib in liver cancer [Pharma Times] Lenvatinib is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode already on certain global markets as a treatment for thyroid cancer, under the brand name Lenvima, and for renal cell cancer, under the brand name Kisplyx (in the EU).
	5.4 Traitements - Economie
NICE approval for nivolumab provides new treatment for advanced blood cancer [NICE] The drug will be used for patients whose cancer is progressing despite having a stem cell transplant from their own cells and treatment with another drug called brentuximab vedotin.
After NICE setback, Roche strikes deal for Gazyvaro coverage in U.K. [Fierce Pharma] To be given in combo with chemotherapy and after treatment with Roche’s Rituxan, Gazyvaro will be available for up to four years as authorities gather more data on its long-term cost effectiveness.
NICE backs Roche’s Gazyvaro for follicular lymphoma [Pharma Times] The committee concluded that the Gazyvaro-based approach is clinically effective, but were uncertain of its overall survival gain, and so recommended its use in the CDF where further evidence can be collected.
	6. Lutte contre les cancers
Finding the signal in the noise of hospital quality metrics [The Incidental Economist] There are valid reasons to be suspicious of measurements of hospital quality. One longstanding concern is that some hospitals may disproportionately attract sicker patients, who are more likely to have worse health outcomes.
	6.1 Observation
Overweight at 17? Your Colon Cancer Risk Rises [NY Times] The analysis, published in the journal Cancer, included just over one million males and 707,212 females. Over a median follow-up of 23 years, the investigators identified 1,977 cases of colon and rectal cancer among the men, and 990 cases among the women.
Adult colorectal cancer risk tied to weight as a teen [Reuters] Long-term follow-up of 1.79 million Israeli men and women examined for military service as teenagers showed that overweight and obese teens were over 50 percent more likely to develop colon or rectal cancer by middle age, compared to normal-weight peers.
	6.11 Patients
What Advances are Researchers Making in Treating Glioblastoma, McCain’s Cancer? [AACR] The clinical trials database of the NIH currently lists 274 studies testing new treatment options for this disease, including immunotherapies such as therapeutic vaccines, immune checkpoint inhibitors, and chimeric antigen receptor (CAR) T-cell therapies.
Dear Sen. McCain: Here’s what I’ve learned from living with glioblastoma [STAT] I worry each day that I may have made the wrong choice and should have opted for the aggressive approach. But the fact that I can walk with minimal instability and can “run” and play with my children on our lawn validates my decision again and again.
	6.3 Associations/Fondations
Cancer Research UK: Taking a broad view of research impact [BioMed Central blog] Cancer Research UK commits to taking a broad view of research impact by accepting preprints in grant applications.
	6.7.2 Applis
FDA Announces New Steps to Empower Consumers and Advance Digital Healthcare [FDA Voice] This new program embraces the principle that digital health technologies can have significant benefits to patients’ lives and to our healthcare system by facilitating prevention, treatment, and diagnosis; and by helping consumers manage chronic conditions outside of traditional healthcare settings.
	6.7.3 DMP
Amazon has a secret health tech team called 1492 working on medical records, virtual doc visits [CNBC] Amazon has started a secret skunkworks lab dedicated to opportunities in health care, including new areas such as electronic medical records and telemedicine. Amazon has dubbed this stealth team 1492, which appears to be a reference to the year Columbus first landed in the Americas.
	6.9 Controverses
New "p < 0.005" Standard Considered Harmful [Multa Verba] The problem is that the vast majority of negative results are never reported, which gives a biased picture of the state of knowledge. By lowering the p-threshold, the file-drawer bias will be even greater, since fewer results, with only lower p-values, are published.