Onco Actu du 6 mai 2019

	1. BIOLOGIE
Muting Mutations [In The Pipeline] We’ve been talking about “penetrance” of genetic disorders without really knowing what we’re referring to in detail, but that’s changing. The transcriptional machinery is startling stuff, and it gets more impressive and complicated the further we dig into it.
Manipulating the tumour-suppressor protein Rb in lung cancer reveals possible drug targets [Nature] Tumours often become resistant to treatment, but how this occurs is poorly understood. An analysis of how the protein Rb affects tumour growth and the response to therapy might cast light on the problem.
	1.4 BIOLOGIE - TECHNOS
New technique by Yale Cancer Center scientists may improve detection and treatment of advanced brain cancer [Yale Cancer Center] Another surprise came when the scientists wondered about how “plastic” tumor cells are in gene expression. When they took lung tumor cells back out of the mice and put them back into cell culture, expression of many genes reverted to baseline levels.
	2.11 ETIOLOGIE - ALIMENTATION
Bacon, salami and sausages: how does processed meat cause cancer and how much matters? [Cancer Research UK] “The data from our study does suggest that eating little to no processed and red meat lowers the risk of bowel cancer, but the increased risk at lower intakes is small so this doesn’t imply that everyone needs to give up meat altogether,” says Key.
	2.6 ETIOLOGIE - ENVIRONNEMENT
Viewpoint: Defending IARC’s designation of glyphosate as carcinogenic undermines evidence-based science [Genetic Literacy Project] Few scientists would dispute that further high-quality studies of glyphosate and glyphosate-containing products might add to our knowledge. But IARC should be held accountable for its cynical misrepresentation of the existing evidence.
U.S. environment agency says glyphosate weed killer is not a carcinogen [Reuters] The EPA’s announcement reaffirms its earlier findings about the safety of glyphosate, the key ingredient in Bayer’s Roundup. The company faces thousands of lawsuits from Roundup users who allege it caused their cancer.
EPA Takes Next Step in Review Process for Herbicide Glyphosate, Reaffirms No Risk to Public Health [EPA] While the agency did not identify public health risks in the 2017 human health risk assessment, the 2017 ecological assessment did identify ecological risks. To address these risks, EPA is proposing management measures to help farmers target pesticide sprays on the intended pest, protect pollinators, and reduce the problem of weeds becoming resistant to glyphosate.
	3.1 PRÉVENTION - TABAC
Quitting Smoking is Associated With Reduced Risk of Bladder Cancer in Postmenopausal Women [AACR] They included data from 143,279 women, all of whom had supplied information on whether they had ever smoked cigarettes, how much they had smoked, and whether they were current smokers.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
F.D.A. Permits the Sale of IQOS, a New Tobacco Device [NY Times] While the agency stopped short of declaring that the device was safer than traditional cigarettes, the F.D.A. did say the heated tobacco-stick system could help people to quit smoking.
FDA permits sale of Philip Morris IQOS tobacco-heating alternative to cigarettes [Reuters] Following a review of about two years, the FDA determined that authorizing the device for sale in the U.S. market was “appropriate for the protection of public health” because the products produce “fewer or lower levels of some toxins than combustible cigarettes.”
In Washington, Juul Vows to Curb Youth Vaping. Its Lobbying in States Runs Counter to That Pledge. [NY Times] The company’s 80-plus lobbyists in 50 states are fighting proposals to ban flavored e-cigarette pods, which are big draws for teenagers; pushing legislation that includes provisions denying local governments the right to adopt strict vaping controls; and working to make sure that bills to discourage youth vaping do not have stringent enforcement measures.
	4.1 DÉP., DIAG. & PRONO. - PROSTATE
A new method to select the right treatment for advanced prostate cancer [Karolinska Institutet] “This suggests that patients with a normal TP53 gene, without or with a small number of AR resistance markers would benefit more from continued hormonal treatment with medicines such as Zytiga and Xtandi.”
New panel of genes identifies men at highest risk of aggressive prostate cancer [Institute of Cancer Research] Scientists at The Institute of Cancer Research, London, analysed the genes of more than 1,200 men with young-onset prostate cancer – in which inheritance is likely to play a particularly important role – and more than 1,100 healthy men.
	4.12 BIOPSIES LIQUIDES
Making the Invisible Visible: New method Opens Unexplored Realms for Liquid Biopsies [University of Michigan] A new approach to RNA sequencing reveals thousands of previously inaccessible RNA fragments in blood plasma that might serve as disease- and organ-specific biomarkers.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
Medical DNA sequencing leads to lawsuits and legal questions [Science] Effort to reconcile law and genomics moves forward as multiyear project LawSeq nears finish line.
	4.7 DÉP., DIAG. & PRONO. - COL DE L'UTÉRUS
Urine test could prevent cervical cancer [University of Manchester] Dr Crosbie said: “These results provide exciting proof of principle that urine HPV testing can pick up cervical pre-cancer cells, but we need to trial it on a greater number of women before it can be used in the NHS.”
	4.9 DÉP., DIAG. & PRONO. - SEIN
Breast cancer relapse test can predict treatment benefits, study suggests [Cancer Research UK] The test, called EndoPredict (EPCyclin), successfully predicted whether chemotherapy would be beneficial for patients with the most common type of breast cancer.
When It's Time For A Mammogram, Should You Ask For 3D? [NPR] Because the technology is relatively new, long-term studies just haven't been done. So the question now, says Smith, is whether 3D technology ultimately results in more lives saved.
	5. TRAITEMENTS
Less-invasive mastectomy is safe option for more breast cancer patients, Mayo Clinic study finds [Mayo Clinic] Researchers evaluated nipple-sparing mastectomy outcomes in 769 women who had the procedure between 2009 to 2017. In all, the surgery was performed on 1,301 breasts during the study period.
Tackling side effects in head and neck cancer treatment – the end of the road for hyperbaric oxygen? [Cancer Research UK] The other big finding was that hyperbaric oxygen had no impact on the number of people developing osteoradionecrosis – the numbers were pretty much the same in each side of the trial.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
New cancer therapy target found in mitochondria for potential treatment of blood cancers [MD Anderson Cancer Center] Study shows how imipridone drugs ONC201 and ONC212 cause cancer cell death.
First U.S. use of CRISPR to directly target cancer will seek go-ahead from regulators [STAT] Kmiec and his colleagues have not yet determined how to deliver CRISPR to tumor cells, a challenge for the entire field. They will either inject CRISPR directly into lung tumors or administer it via infusion into the blood, packaged in adeno-associated viruses (AAVs).
An EGLN Inhibitor Protects Normal Tissues and Enables High-dose Radiation Therapy in a Mouse Model of Unresectable Pancreatic Cancer [AACR] “While we utilized EGLN inhibitors in our study, we want to emphasize that radioprotection is not limited to this class of drugs,” noted Taniguchi. “We hope that our results stimulate more research in this area.”
	5.10 TRAITEMENTS - ESSAIS
European universities dismal at reporting results of clinical trials [Nature] “Major universities in continental Europe are clearly not investing the effort required to meet their ethical, scientific and regulatory obligations,” says report author Till Bruckner, of the UK-based transparency campaign group TranspariMED.
EU universities are miserably lax at reporting clinical trial results, analysis suggests [EndPoints] None of the assessed universities in France, Italy, Norway and Sweden have made a single clinical trial result public on the registry, the report found.
	5.12 IMMUNOTHÉRAPIES
The entrepreneur behind the cancer immunotherapy revolution [STAT] Lonberg was not on the podium in Oslo that day; nor was Korman. But, without them, the class of medicines now known as checkpoint inhibitors — which have changed the way doctors think about tumors and which now are used to treat skin, lung, kidney, and other cancers — might not exist.
Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs [JAMA Network Open] This cross-sectional study found that the estimated percentage of US patients with cancer who are eligible for checkpoint inhibitor drugs increased from 1.54% in 2011 to 43.63% in 2018. The percentage of patients estimated to respond to checkpoint inhibitor drugs was 0.14% in 2011 and increased to 12.46% in 2018.
	5.12.1 IMMUNOTHÉRAPIES - PARTENARIATS
AstraZeneca ups oncolytic virus activity with Transgene deal [Fierce Biotech] Oncolytic viruses have undergone a renaissance in recent years as leading drug developers such as Boehringer Ingelheim, Johnson & Johnson and Merck have identified them as a way to broaden the efficacy of immuno-oncology agents.
Transgene and AstraZeneca enter into a collaboration and exclusive license option agreement for innovative Invir.IO(TM) based armed oncolytic immunotherapies [Transgene] Under the terms of the agreement Transgene will contribute its oncolytic virus expertise, including viral design and engineering, to the collaboration as well as its novel and improved Vaccinia Virus (TK-, RR-) double-deleted backbone and will be responsible for in-vitro pre-clinical development.
AstraZeneca ties up with France's Transgene to develop viral immunotherapies [Reuters] Viral immunotherapy represents a new way of treating cancer by using transgenes, or genes that are artificially introduced into the genome of another organism.
AstraZeneca bets cautiously on oncolytic virus discovery program, outlining $13M deal with Transgene [EndPoints] In the deal, the biotech — which is already allied with Bristol-Myers Squibb and Pfizer/Merck KGaA on combination programs with its in-house therapeutic vaccines — will come up with five new armed oncolytic vaccinia virus candidates.
	5.12.11 IMMUNOTHÉRAPIES - PRÉ-CLINIQUE
Fighting colon cancer with killer cells [DKFZ] They are making use of a new approach in cancer immunotherapy: genetically modified natural killer cells. Using patient-specific tumor cultures, scientists can now run tests in the lab to see how effective the killer cells will be in individual patients.
Research decodes one way cancer survives treatment, proposes a way to prevent it [Mayo Clinic] What they discovered is that inside the cell, PD-L1 is used to promote repair during chemotherapy or radiation therapy. Their article is the first to report on this internal use, defining a new function for PD-L1 as an RNA-binding protein.
Tumor-selective angiotensin blockers may improve response to cancer immunotherapy [Mass. General Hospital] As described in their report published in PNAS, the combination treatment significantly improved tumor response and survival in several mouse models of breast cancer, one of several types of solid tumor that have resisted the effects of immunotherapy.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Celgene reports 'durable' responses to multiple myeloma CAR-T in early trial despite relapses [Fierce Biotech] Celgene’s CAR-T is playing in a crowded field of drugs and other cell therapies for multiple myeloma with the same target, BCMA.
Phase 1 interim results for anti-BCMA CAR T-cell therapy in relapse refractory multiple myeloma [ecancer news] Treatment with bb2121 resulted in an 85% objective response rate (ORR) with 45% of patients achieving a complete response (CR) (n=15) and an additional 27% of patients (n=9) achieving a very good partial response (VGPR) to yield a ≥ VGPR rate of 73%.
Tessa showcases preclinical promise of ‘all-in-one’ add-on to its cancer cell therapy, in march to the clinic [EndPoints] The treatment, which is tailored for HER2-positive solid tumors, consists of two steps: First, investigators inject an oncolytic adenovirus into a tumor site, simultaneously killing tumor cells and secreting PD-L1 blocking antibodies and IL-12p70 cytokines. Then comes the CAR-T, which pillages the region systemically to clear out other cancer cells.
New Experimental Therapy CAR NKT-Cells Tested In Cancer Patients For The First Time [Forbes] The CAR-NKT cell treatment CMD-501, developed by UK-based cellular therapy company Cell Medica is the first of its kind to ever be trialed in any disease.
	5.12.3 IMMUNOTHÉRAPIES-COMBINAISONS
Personalized Combination Therapies Yield Better Cancer Outcomes [NIH Director's Blog] 73 participants received a customized combination therapy. As no two molecular profiles were identical, the customized treatment regimens varied from person to person. Many people received designer drugs targeting particular genetic alterations. Some also received checkpoint inhibitor immunotherapies to unleash the immune system against cancer.
	5.12.4 IMMUNOTHÉRAPIES - ESSAIS
Merck's Keytruda stumbles again in stomach cancer, this time in new patients [Fierce Pharma] Merck won’t share the details of the miss until June’s American Society of Clinical Oncology annual meeting, but its senior vice president and head of global clinical development, Dr. Roy Baynes, did note that “gastric cancer is historically difficult to treat.”
	5.12.5 IMMUNOTHÉRAPIES - PHARMA
Tmunity boosts pipeline with childhood brain cancer treatment from UCSF [Fierce Biotech] If all goes well, a new T-cell receptor (TCR) treatment for a fatal type of brain cancer could be in the clinic by 2021, said Tmunity CEO Usman “Oz” Azam.
	5.12.8 IMMUNOTHÉRAPIES - ECONOMIE
Atezolizumab in combination for treating metastatic non-squamous non-small-cell lung cancer [NICE] It is recommended only if the company provides atezolizumab and bevacizumab according to the commercial arrangements.
Roche's Tecentriq-Avastin lung cancer combo gets a lift from England's cost watchdogs [Fierce Pharma] Even with the restrictions, the NICE decision opens up treatment for 4,800 patients in England, according to Roche’s estimates.
	5.2 PHARMA
J&J eyes prostate cancer boost as FDA accepts Erleada for real-time review [Fierce Pharma] The news follows J&J’s January announcement that investigators had halted a phase 3 study of Erleada, combined with androgen deprivation therapy (ADT), after the regimen showed it could significantly stave off disease progression and lengthen lives.
Janssen Submits Application to U.S. FDA Seeking Approval of ERLEADA® (apalutamide) for Patients with Metastatic Castration-Sensitive Prostate Cancer [Janssen] Supplemental New Drug Application Supported by Phase 3 TITAN Study; Submitted Through FDA Real-Time Oncology Review Program.
U.S. FDA accepts new drug application and grants priority review for darolutamide [Bayer] The NDA and Priority Review status were based on data from the Phase III ARAMIS trial in men with nmCRPC.
FDA tags Bayer’s prostate cancer drug for priority review as drugmaker gears up against rivals [EndPoints] Like Pfizer’s Xtandi and J&J’s Erleada, darolutamide is a non-steroidal androgen receptor inhibitor for prostate cancer patients whose disease has not spread but continues to grow despite low testosterone levels.
	5.2.1 PHARMA - PARTENARIATS
Novartis's Sandoz strikes deal for biosimilar of Herceptin [Reuters] The deal - the third biosimilar collaboration for Sandoz in 18 months - expands the existing Sandoz cancer portfolio of four oncology biosimilar medicines.
Celgene taps Presage's microdosing tech for phase 0 cancer studies [Fierce Biotech] The platform, called CIVO, is designed to assess patients’ unique response to microdoses of multiple cancer drugs. It is Presage’s solution to a fundamental problem in cancer drug development—the failure of preclinical animal models to accurately predict how drugs will perform in humans.
	5.2.3 PHARMA - ÉCONOMIE
Lilly dumps phase 2 cancer drugs that survived previous cull [Fierce Biotech] The Big Pharma revealed in its first-quarter earnings presentation that it is dumping a PI3K/mTOR dual inhibitor it was developing for use in combinations and prexasertib, the CHK1 inhibitor it picked up from Array BioPharma.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
Substandard control arms question the utility of some new cancer drugs [STAT] The take-home message from our analyses is that FDA approval doesn’t automatically make a new drug better than treatments doctors are currently using. Take, for example, the case of ibrutinib, a drug the FDA approved for treating chronic lymphocytic leukemia.
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
LYNPARZA® (olaparib) Receives Positive EU CHMP Opinion for First-Line Maintenance Treatment in BRCA-Mutated Advanced Ovarian Cancer [Merck] AstraZeneca and Merck’s LYNPARZA Is the Only PARP Inhibitor in This Setting to Demonstrate an Improvement in Progression-Free Survival for Patients Who Responded to Platinum-Based Chemotherapy.
FDA approves Roche’s Kadcyla for adjuvant treatment of people with HER2-positive early breast cancer with residual invasive disease after neoadjuvant treatment [Roche] The approval is based on data showing Kadcyla cut the risk of disease recurring by half compared to Herceptin in the adjuvant setting for specific patients with HER2-positive early breast cancer.
EMA Recommends Granting a Marketing Authorisation for Talazoparib [ESMO] It received a positive opinion for the treatment of adult patients with germline BRCA1/2 mutations who have HER2-negative locally advanced or metastatic breast cancer.
Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 23-26 April 2019 [EMA] The CHMP recommended the granting of a conditional marketing authorisation for Libtayo (cemiplimab), for the treatment of advanced cutaneous squamous cell carcinoma. Talzenna (talazoparib) received a positive opinion for the treatment of adult patients with germline BRCA1/2 mutations who have HER2-negative locally advanced or metastatic breast cancer.
EMA Recommends Withdrawal of Marketing Authorisation for Olaratumab [ESMO] The results of the ANNOUNCE study show that olaratumab with doxorubicin does not prolong the lives of patients with soft tissue sarcoma.
EMA recommends withdrawal of marketing authorisation for cancer medicine Lartruvo [EMA] At time of its approval, data on the effects of Lartruvo were limited because of the small number of patients included in the main study which supported authorisation. The medicine was therefore granted a marketing authorisation on condition that the company provided additional data from the ANNOUNCE study in order to confirm the benefits and safety of the medicine.
Pfizer Receives Positive CHMP Opinion for TALZENNA® (talazoparib) for Patients with Inherited (Germline) BRCA-Mutated Locally Advanced or Metastatic Breast Cancer [Pfizer] Positive opinion based on results from largest Phase 3 trial performed to date of a PARP inhibitor in gBRCA-mutated advanced breast cancer.
	5.6.6 ESMO - SEIN
Molecular Analysis of Samples from the AURORA Programme Is Underway [ESMO] Integrated molecular analyses shed light on alterations correlated with disease progression and therapeutic resistance in metastatic breast cancer.
The AURORA international academic research programme [BIG] The initial results of AURORA were announced at the ESMO Breast Cancer Congress held on 2-4 May 2019 in Berlin, Germany. Dr Philippe Aftimos presented the results for the first 381 patients included out of a planned total of 1,000. The researchers have identified molecular alterations present in excess in metastases that may be correlated with the spread of cancer and increased resistance to standard treatments.
	6.1 OBSERVATION
Elderly Survivors of Three Common Cancers Face Persistent Risk of Brain Metastasis [AACR] In this study, researchers analyzed rates of synchronous brain metastases (SBM), those diagnosed during the staging workup for the primary cancer, and lifetime brain metastases (LBM), those diagnosed later in life. Primary cancers in this study were lung cancer, breast cancer, and melanoma, which are more likely to metastasize to the brain than many other cancer types.
Cancer patients waiting to see a specialist in record numbers this winter [The Telegraph] Doctors’ leaders have condemned the “shameful” state of cancer services this winter, as it emerged the number of patients waiting to see an oncologist for more than three weeks jumped 73 per cent compared to the year before to more than 8,800.
	6.10.1 POLITIQUES (USA)
Trump’s science adviser on research ethics, immigration and presidential tweets [Nature] Does it make your job as science adviser harder when Trump tweets and talks about things such as windmill noise causing cancer?
	6.11 PATIENTS
Almost half of people diagnosed with cancer find it hard to ask for help, as many fear being pitied [Cancer Research UK] Even though nearly half of those diagnosed with cancer reported they struggled to open up, 43% of respondents agreed they felt better once they had spoken to their loved ones about how they were feeling.
A rising trend in cancer care targets physical, existential threats patients confront [Washington Post] Palliative method targets the “whole-person” using mind-body practices, massage, stress and symptom management: “If I don’t live long, I want to make sure I live my best life.”
	6.2 IMPLANTS MAMMAIRES
Statement from FDA Principal Deputy Commissioner Amy Abernethy, M.D., Ph.D., and Jeff Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health on FDA’s new efforts to protect women’s health and help to ensure the safety of breast implants [FDA] We are also announcing today a change in how breast implant manufacturers file medical device reports with the FDA.
FDA won’t ban breast implants linked to cancer at this time [Washington Post] A month after a dramatic hearing in which many women called on the Food and Drug Administration to ban a type of breast implant linked to a rare cancer, the agency said it won’t take that action now.
F.D.A. Won’t Ban Sales of Textured Breast Implants Linked to Cancer [NY Times] Jamee Cook, co-founder of Breast Implant Victim Advocacy, said she was disappointed that textured implants will not be banned. But she welcomed the F.D.A.’s proposals to ensure patients are better informed about the potential risks of breast implants.
	6.6 PUBLICATIONS
Too Much Wasted Time [In The Pipeline] The author (Dorothy Bishop) has, unfortunately, some very good points. The good news, though (as she mentions) is that reproducibility is finally being taken more seriously.
	6.7 DMP, BIG DATA & APPLIS
‘Deep medicine’ will help everyone, especially people like me with a rare disease [STAT] Neither of us is knocking people power. But with the vast amount of existing medical data and the explosion of new data, deep medicine promises to put humans in charge, augmented by smart machines.
Is useful research data usually shared? An investigation of genome-wide association study summary statistics [bioRxiv] Thus, data sharing is the exception even in suitable research fields with relatively strong norms regarding data sharing.
	6.7.1 IA/BIOINFORMATIQUE
The proof of the pudding: in praise of a culture of real-world validation for medical artificial intelligence [Annals of Translational Medicine] Among these different kinds of validity, we distinguish between statistical validity, relational validity, pragmatic validity and ecological validity. To better understand the characteristics of these four kinds of validity, we must first take a step back.
If pharma looks slow to adopt AI, it's got good reason, expert says [Fierce Pharma] “The results of a misprediction on your GPS on the phone is going to result in 15 minutes’ delay, or an hour delay. It’s not going to be hundreds of millions (of dollars), and it would not cost lives of patients,” David Harel, CEO of machine learning company CytoReason, said.
The Cutting-Edge Of AI Cancer Detection [Forbes] AI faces its own unique challenges in this field - such as the lack of enough data to train neural networks - but companies on the cutting-edge of cancer detection are finding novel ways to get around the problems, and achieving impressive results.
AI Uses Images and Omics to Decode Cancer [The Scientist] Machine learning can analyze photographs of cancer, tumor pathology slides, and genomes. Now, scientists are poised to integrate that information into cancer uber-models.
	6.9 CONTROVERSES
Chinese hospitals set to sell experimental cell therapies [Nature] Select elite hospitals in China could soon be able to sell experimental therapies that engineer a patient’s own cells to treat diseases such as cancer — without approval from the nation’s drug regulator.
'Maverick' doctor used experimental cancer treatment on 10 patients who died, inquest to hear [The Telegraph] A coroner is to investigate the deaths of the patients who died after they were treated by Paul Miller between 2007 and 2013, as well as claims that hospital bosses took five years to react to concerns from colleagues.