Onco Actu du 28 février 2019

	1. BIOLOGIE
Cancer genes’ age and function strongly influence their mutational status [eLife] Novel insights on early cancer genes and their role in the human gene regulation network could aid future development of potential new cancer treatments.
HeLa Cells from Different Labs Vary in Genetics, Phenotype [The Scientist] This latest investigation is the first comprehensive analysis of genetic variation across a wide range of HeLa variants—different batches of HeLa cells that live in various labs around the world—and the first to demonstrate that the genetic heterogeneity results in changes in protein expression and phenotype.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
Yes we can, EUCANCan! [VHIO] A total of 18 partners with aligned strategies have joined forces as a carefully pieced model to provide a functional platform for federated genome analysis systems towards efficiently analyzing, managing, sharing and reusing mass genomic data at a global level.
	5. TRAITEMENTS
Proteasome Inhibitors, Refined [In The Pipeline] Now, this list might be seen as an egregious example of “me-too” drugs gone crazy. How, you wonder, did the world end up with so many proteasome inhibitors, especially since several of them look so similar to others in the same class? Because they’re still different.
Lab-grown mini tumors could help identify personalized treatments for people with rare cancers [UCLA] New technique developed at UCLA can screen hundreds of drugs using patients’ own cells.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
Blocking DNA repair restores sensitivity of brain tumors to treatment in mice [NIH] The researchers found that they could extend the lives of mice with the mutant IDH1 tumors by exposing them to radiation while also injecting them with one of two compounds designed to block DNA repair. In contrast, treating these mice with either radiation or either of the drugs alone had no effect.
	5.10 TRAITEMENTS - ESSAIS
AstraZeneca, Merck's Lynparza posts pancreatic cancer win in another PARP-class first [Fierce Pharma] If the companies can eventually snag a green light, it will make Lynparza the first PARP drug to break into pancreatic cancer, which bears the worst survival rate among the most common cancers.
AstraZeneca's PARP drug succeeds in pancreatic cancer study [Biopharma Dive] The late-stage study enrolled 154 patients and gave them either 300 mg of Lynparza twice daily or placebo. While more data is needed to contextualize the magnitude of Lynparza's benefit in this setting, AstraZeneca leadership signaled confidence in the topline results issued Wednesday.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Immatics, Roche ally to trial Tecentriq with cell therapy [Fierce Biotech] IMA101 consists of cytotoxic T lymphocytes selected to recognize up to four targets expressed by the patient’s tumor. By expanding the cells and readministering them back into the patient, Immatics thinks it can create treatments that overcome the relapse and target specificity problems that have stopped adoptive cellular therapies from gaining traction in solid tumors to date.
Scientists devise strategies to counteract T cell exhaustion in CAR T cancer therapies [La Jolla Immunology] La Jolla Institute scientists show that deleting troublesome proteins in a mouse model can shrink tumors and prolong survival.
Driving CAR T cell translation forward [Science Translational Medicine] Successes in CAR T cell translation have propelled their commercial launch, but expanding the impact of cancer immunotherapies remains challenging.
	5.2 PHARMA
Parexel, on a hiring spree, nabs another key FDA staffer as it bolsters oncology execs [Fierce Biotech] Not content with hiring four former FDA staffers this month, Parexel is at it again, nabbing another top ex-FDA executive and promoting a former medical oncologist to boost its cancer drug development services.
Parexel recruits top FDA oncology expert Amy McKee for new R&D initiative [EndPoints] During McKee’s 11-year career at the FDA, she’s held a frontrow seat to multiple breakthroughs from reviewing olaparib — the pioneering PARP inhibitor now known as Lynparza — to stamping the final seal of approval for Loxo’s tissue agnostic cancer drug.
	5.2.1 PHARMA - PARTENARIATS
Servier terminates CTI cancer pact following clinical failure [Fierce Biotech] Servier has terminated its Pixuvri collaboration agreement with CTI BioPharma. The action comes seven months after the B-cell non-Hodgkin lymphoma drug failed a key clinical trial.
	5.2.2 PHARMA - FUSIONS & ACQUISITIONS
Bristol-Myers’ largest shareholder comes out against its $74B Celgene buyout, raising a ‘real risk’ of torpedoing the deal [EndPoints] Celgene shares plummeted more than 10% after the news spread Wednesday evening. Bristol-Myers shares, meanwhile, rose 2.6%.
Top Bristol-Myers shareholder comes out against $74 billion Celgene deal [Reuters] Wellington Management, which owns about 8 percent of Bristol-Myers shares, said it found the Celgene deal to be too risky and expensive. It said other options to create value for shareholders “could be more attractive.”
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
FDA experts turn thumbs down on Karyopharm’s troubled pitch for an accelerated OK — but not all of them [EndPoints] The panel voted 8 to 5 against an approval of selinexor for multiple myeloma, saying affirmatively that the FDA should take a wait-and-see attitude until the randomized pivotal study wraps toward the end of the year.
	5.9 AACR
Prostate Cancer Patients With Cardiovascular Disease Had Higher Mortality After Starting Abiraterone Acetate [AACR] Patients with advanced prostate cancer who had pre-existing cardiovascular disease had higher risk of mortality in the six months after starting abiraterone acetate (Zytiga) treatment compared with those who had no pre-existing cardiovascular disease, according to data presented during a media preview of the AACR Annual Meeting 2019, which will be held March 29–April 3, in Atlanta.
	5.9.10 AACR - COLORECTAL
Survey of Young-onset Colorectal Cancer Patients Suggests Misdiagnosis May Be Common [AACR] In this study, the Colorectal Cancer Alliance conducted a comprehensive survey of young-onset patients and survivors to gather further information about their clinical, psychosocial, financial, and quality-of-life experiences.
	5.9.12 AACR - BIOPSIES LIQUIDES
Liquid Biopsy-based Test As Good As Tissue-based Test for Identifying Treatment for Lung Cancer [AACR] The NILE study also found that the cfDNA test results of four biomarkers (EGFR, ALK, ROS1, BRAF), for which there are U.S. Food and Drug Administration-approved drugs, were concordant with the tissue-based test results, with a positive-predictive value of 100 percent.
Guardant’s blood test might replace biopsies for some lung cancer patients, study says [STAT] In other words, the blood test was more likely to match patients with drugs. It was also much faster. Results arrived in nine days with the Guardant blood test compared to 15 for the biopsy patients, meaning that very sick patients could start treatment sooner.
	5.9.9 AACR - IMMUNOTHÉRAPIES
Dietary Factors Affecting Gut Microbiome May Influence Response to Immunotherapy in Melanoma Patients [AACR] “There’s a perception that taking probiotics improves gut health, but our results, although early, suggest that may not be the case for cancer patients.”
	6. LUTTE CONTRE LES CANCERS
Data sharing will be a major thrust of Trump’s $500 million childhood cancer plan [Science] That plan is getting a mixed response from researchers and patient advocates, who also worry that the initiative will come at expense of other parts of the National Cancer Institute’s (NCI’s) budget.
	6.1 OBSERVATION
Hyperglycemia and Aggressive Prostate Cancer Risk [Cancer Research Catalyst] “We saw that hyperglycemia was not associated with total prostate cancer incidence, but it was positively associated with a lethal cancer phenotype,” noted Joshu. “We found a fairly pronounced pattern of association.
Nearly half of all children with cancer go undiagnosed and untreated [Thee Guardian] The research suggests that the situation depends on location: while only 3% of childhood cancer cases in western Europe and north America are thought to have been missed in 2015, the proportion rose to an estimated 49% in south Asia and 57% in western Africa.
	6.10.1 POLITIQUES (USA)
In muted hearing, pharma execs dodge attempts to pin blame for high prices [STAT] Though both Democrats and Republicans had repeatedly warned pharmaceutical executives against shifting blame to other players in the supply chain, many of the drug industry executives did so anyway.
Pharma companies want the government to do something about high drug prices, so long as it's not forcing them to lower their drug prices [Business Insider] On Tuesday, seven top executives from pharmaceutical companies made a case forwhy it's not in their control to lower the price of the prescription drugs they sell. Instead, at a hearing held by the Senate Finance Committee, they pointed the finger at other parts of the healthcare system.
In landmark hearing, drugmakers and lawmakers agree that US policy on drug pricing is ripe for change — but there’s no consensus on much else [EndPoints] At the end of the proceedings, the panelists largely agreed. The “government has to step up and change the rules,” Soriot said. Now there’s just the small matter of figuring out how to do that.
U.S. senators tell drug company executives pricing is 'morally repugnant' [Reuters] U.S. senators called drug pricing practices “morally repugnant” and told drug company executives they do not want to hear them blame others for the high prices, taking an aggressive stance at a Senate hearing on the rising costs of prescription medicines.
	6.4 MÉDICO-ÉCO
Cancer Complications: Confusing Bills, Maddening Errors And Endless Phone Calls [NPR] Coping with the financial fallout of cancer is exhausting — and nerve-wracking. But the worst part, Marley says, is that it's unexpected.
	6.6 PUBLICATIONS
High-profile subscription journals critique Plan S [Nature] Publishers say that the bold open-access initiative rules out proven ways of opening up the literature.
	6.8 COMMUNICATION
Netflix pulls controversial documentary that claims root canals cause cancer [The Guardian] The film, directed by Australian film-maker Frazer Bailey, alleges that root canals cause cancer, heart disease and other serious chronic illness, and that the best way to deal with an injured or infected tooth would be to simply pull it. These claims have no scientific basis.
	6.9 CONTROVERSES
Simon Rule and Steven LeGouill: Bureaucracy is strangling clinical research [BMJ] This opinion piece has been signed by almost 1000 senior researchers in haematology from across Europe. Most have been involved with clinical research for years and are fortunate in having research teams around them that help with this ever-increasing workload, but for new investigators without any infrastructure to support them clinical research has become too time consuming and challenging to engage with.