Onco Actu du 6 avril 2017

	1. Biologie
CRISPR studies muddy results of older gene research [Nature] The literature suggested that the gene MELK was ideal: there was ample evidence that it is important in cancer-cell proliferation, and clinical trials are under way to test drugs that inhibit the MELK protein. But disabling the gene using CRISPR–Cas9 yielded no effect. “That threw a monkey wrench into our experiments,” says Sheltzer. “It brought everything to a halt.”
	3.1 Tabac
FDA Warns Pfizer Clinical Investigator Over Chantix Study [RAPS] Following an inspection at the clinical site between 15 August 2016 and 14 September 2016, FDA says in the letter that Indianapolis-based Cassandra Curtis, MD, failed to adhere to the investigational plan’s protocol requiring certain subjects to be excluded and other requirements on the use of certain medications.
Smoking causes one in 10 deaths worldwide, study shows [BBC News] Smoking causes one in 10 deaths worldwide, a new study shows, half of them in just four countries - China, India, the US and Russia. Despite decades of tobacco control policies, population growth has seen an increased number of smokers, it warned.
Smoking causes one in ten deaths globally, major new study reveals [The Guardian] Efforts to control tobacco have paid off, says study, but warns tobacco epidemic is far from over, with 6.4m deaths attributed to smoking in 2015 alone.
	4.1 Dép., diag. & prono. - Prostate
Guys: you don't need a PSA test for prostate cancer [Genomics, Medicine, and Pseudoscience] I learned a new word this week: pseudoepidemic. That's what happens when people start looking really hard for a disease that didn't get much attention earlier, and then–not surprisingly–the disease suddenly becomes much more prevalent.
	4.13 Dép., diag. & prono. - Peau
Pivotal Study Results for Myriad's myPath® Melanoma Test Highlighted In Two Additional Scientific Publications [Myriad] The Company Will Seek Reimbursement from Medicare and Private Payers.
	5. Traitements
Taking Shortcuts In Drug Testing Can Put Patients At Risk [NPR] The solution to speeding breakthroughs in medicine is not to take shortcuts in evidence generation, but to leverage emerging methods and networks that can potentially generate robust clinical evidence faster, cheaper and better. In a digital age, we can push for better evidence without sacrificing much time.
	5.12 Immunothérapies
Cancer immunotherapy: more reason for concern? [HealthNewsReview] During the honeymoon period there was no shortage of press releases, headlines, and advocates more than ready to endorse immunotherapy with those highly clickable 7 words (cure, breakthrough, miracle, etc.) … but now that the scrutiny phase has kicked in … the enthusiasm for explaining negative outcomes, caveats, and limitations seems to wane at exactly the time when we need more information presented with more care.
	5.12.2 Immunothérapies - CAR-T
Novartis Keeps 'JULIET' Study Results Close as Investors and Rival Kite Pharma Wait [The Street] That gives Novartis a lot of leeway in how it chooses to disclose the JULIET study results -- to the frustration of everyone else who really wants to know how CTL019 matches up against Kite's axi-cel in DLBCL.
	5.12.5 Immunothérapies - Pharma
Will AACR news give BMS cancer linchpin Opdivo a boost? That depends, analysts say [FiercePharma] Because we don’t know everything about how immuno-oncology drugs work, we also don’t know which are the best biomarkers to use to sift out patients best matched with particular therapies, Divan said.
	5.3 Traitements - FDA, EMA, NICE...
Regulatory Review of New Therapeutic Agents — FDA versus EMA, 2011–2015 [NEJM] The total review times were shorter at the FDA than at the EMA for therapeutic agents that are used for the treatment of cancer and hematologic disease, but not for other therapeutic areas, and for therapeutic agents that were designated as orphan drugs.
NCCN Statement on FDA Leadership and Vision for the Future [National Comprehensive Cancer Network] NCCN looks forward to working with the future FDA Commissioner to ensure that as therapies and products are approved, NCCN can continue to promote the importance of continuous quality improvement through updates to the NCCN Guidelines, NCCN Compendium, and other derivative products.
FDA Nominee Scott Gottlieb To Anti-Vaccine Crowd: Get Over It [Xconomy] Gottlieb, who has often used his position at conservative think tank American Enterprise Institute to pen op-eds about FDA matters such as sluggish drug approvals, generic drug rules, and off-label drug promotion, said he would do nothing to “besmirch” the agency.
FDA nominee says agency must strike right balance between risk, regulation [STAT] She also asked Gottlieb to ensure the FDA would exercise independent, science-based decision-making, and expressed doubt that, in the Trump administration, such a thing would be possible. But Gottlieb promised that under his watch that would be his goal.
Trump nominee to lead FDA questioned on ties to pharmacy industry [Reuters] Gottlieb, who held a financial interest in the vape shop Kure, said some e-cigarettes may have the potential to wean smokers off combustible cigarettes and be less harmful. "An e-cigarette or vaping product might be a good smoking cessation tool while a chocolate chip-flavored e-cigarette might not be," he said.
F.D.A. Nominee Deflects Criticism About Ties to Drugmakers at Hearing [NY Times] He told Congress that, if confirmed, he would be “an absolutely objective regulatory watchdog” and would not do anything that could “besmirch the agency” or undermine public confidence in its work.
With Brexit underway, EU drug agency prepares to leave London [Reuters] Central to keeping staff and minimizing disruption will be picking a new location with good transport links and infrastructure. Rasi dismissed the need for a local science or pharmaceuticals industry base as "irrelevant".
Gottlieb At the FDA [In the Pipeline] From the outside, it looks like FDA approval must be the rate-limiting step for drug approval, but it isn’t. The mental picture of a giant dammed-up lake of wonderful therapies, held back by a huge concrete bureaucracy that allows only a mocking trickle to get through at any one time – is wrong.
	5.9.3 AACR - mélanome
Interim Phase 2 Data Demonstrate Robust Response Rate with Indoximod in Combination with Keytruda® (pembrolizumab) for Patients with Advanced Melanoma at AACR Plenary [NewLink Genetics] 59% Objective Response Rate (ORR) and 80% Disease Control Rate (DCR) in 51 Patients with Non-ocular Melanoma.
	5.9.4 AACR - poumon
Immunomedics says IMMU-132 hits targets in small cell lung cancer [FierceBiotech] The small trial of IMMU-132—also known as sacituzumab govitecan—involved 53 patients with advanced metastatic SCLC who had already been heavily treated with conventional chemotherapy but whose disease was still progressing. All told, out of 49 evaluable patients there were 7 partial responses and 21 people in whom the disease stabilized, according to the AACR abstract.
	5.9.5 AACR - CAR-T
Immunotherapy for ovarian cancer shows promise in mouse model, but hurdles remain [Fred Hutch] ‘Tumor microenvironment’ poses unique challenges for T-cell therapy in solid tumors.
	5.9.6 AACR - prostate
New Form of Therapeutic Shows Efficacy Against Castration-resistant Prostate Cancer in Preclinical Studies [AACR] PROTACs are small molecules with two heads – one side of the small molecule binds to the protein of interest and the other side binds to E3 ubiquitin ligase, which plays a role in a cellular process that signals the degradation of the protein.
	5.9.7 AACR - divers
AACR: 4 Ways surgery will augment molecular medicine to fight cancer [Colorado Cancer Blogs] “I can imagine a day when a patient could take a drug to immediately kill a large primary tumor. But we’re not there yet,” says symposium chairman Dan Theodorescu, MD, PhD, director of the University of Colorado Cancer Center.
Radiation may promote cancer risk by changing selective pressures [Colorado Cancer Blogs] “Therapy doesn’t necessarily cause p53 mutations; therapy selects for p53 mutations.”
Cancer Burden May Be Changing for People Living With HIV [AACR] Cancers typically associated with AIDS are decreasing, but an aging population is likely to see an increase in prostate, lung, and other cancers.
	6.10.1 Politiques (USA)
How the GOP Could Use Science’s Reform Movement Against It [The Atlantic] The principles of openness, transparency, and reproducibility might be weaponized to defund and deny research.
	6.12 Ethique
Star pediatric oncologist committed misconduct, ethical violations: reports [Retraction Watch] The recent news reports allege that Van Gool started some clinical trials without proper ethical approvals and informed consent, and may have misled patients and their families about the benefits and potential side effects of his experimental treatment.
Some Thoughts on the New Common Rule for Human Subjects Research [Genomics Law Report] The bottom line appears to be that, however the Common Rule treats biospecimens, the research world will still be awash in unwittingly donated—and not anonymized—tissue samples. This makes the anguish over the Final Rule, and the ethical aversion to our contractual model, seem like rearranging the deck chairs on the Titanic.
	6.6 Publications
Most citations to retracted papers don’t note they’re problematic, authors say [Retraction Watch] Publishers use software to test for plagiarism. Checking for retractions is much simpler. There are only a few thousand retracted articles. So it is not difficult to create a database that lists all these articles, and to develop a tool that automatically checks whether there are retracted articles in the reference list.