Onco Actu du 1er avril 2019

	1. BIOLOGIE
‘Jumping genes’ drive many cancers [WUSTL] Wang and his colleagues found that many cancers that get switched into overdrive and boost tumor growth have jumping genes that function as a kind of stealthy “on switch.” These cryptic switches can force a gene to be turned on all the time, even though it should be off.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
Vape Nation: Vaping Is Bad, Kids [Science-Based Medicine] The Surgeon General declared youth e-cigarette use to be an epidemic, but many vaping communities online downplay the risks. What does the evidence show?
	4.12 BIOPSIES LIQUIDES
AstraZeneca Liquid Biopsy Comparison Publication Details Concordance Failures [Genome Web] Li added that the data highlights that "many vendors who claim super low detection rates may be reporting false positives, in one case even more false positives than true positives. "We believe a false positive is the worst thing we can do," he added.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
Mopping Up Excess Chemotherapy Drugs [The Scientist] Proof-of-principle tests showed that when placed in the iliac vein in the lower abdomen of live pigs, the device effectively captured more than two-thirds of the doxorubicin infused a short distance upstream.
Researchers target metastasis in fight against cancer [University of Alberta] Scientists at the University of Alberta used two drugs together to enhance DNA damage to human breast cancer cells in mice and reduce their capacity to repair themselves. By doing so, the researchers were able to dramatically shrink tumours and prevent metastasis in the mice.
	5.10 TRAITEMENTS - ESSAIS
Improving the Design of Pivotal Clinical Trials [Clinical Advances in Hematology & Oncology] If the initial approval is based on a surrogate endpoint, then the full approval should measure survival or quality of life. Many drugs therefore come to the market without any proof that they improve survival or quality of life, and they remain on the market for many years without that proof. This is problematic.
	5.12 IMMUNOTHÉRAPIES
Contending with Resistance in Cancer Immunotherapy [The Scientist] Researchers describe ways to study how cancer cells evade therapies that harness the immune system.
	5.12.8 IMMUNOTHÉRAPIES - ECONOMIE
Keytruda nabs key lung cancer nod in China. But are blockbuster sales really attainable? [Fierce Pharma] The Chinese lung cancer market for PD-1/L1s is not as big as some have projected, and without head-to-head studies, Keytruda will have a hard time fighting off several cheaper domestic drugs.
	5.2.1 PHARMA - PARTENARIATS
AstraZeneca inks ambitious $6.9B deal for Daiichi cancer therapy [Biopharma Dive] To help fund the deal, the British pharma aims to raise $3.5 billion via a stock placement with new and existing institutional investors.
	5.2.2 PHARMA - FUSIONS & ACQUISITIONS
Bristol-Myers scores critical endorsements for its embattled Celgene merger [STAT] Combined, ISS and Glass Lewis control about 97 percent of the market for shareholder advice, issuing closely watched recommendations that can sway how major investors vote on executive pay, board elections, and corporate mergers.
Boehringer Ingelheim Enhances Oncology R&D with Novel MacroDel Delivery Technology Via Acquisition of ICD Therapeutics [Boehringer Ingelheim] ICD’s MacroDel technology exploits transporter proteins in the cell membrane to deliver such drug candidates inside tumor cells. This opens up therapeutic targets that would be otherwise inaccessible.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
Scott Gottlieb reflects on his tenure before joining the club of ex-FDA chiefs [Fierce Biotech] One of his main worries, Gottlieb said, was the idea of catastrophic risks being widely distributed before the FDA caught wind of them. While it’s gotten very good spotting early signals in drug therapies, those fears remain on the food and blood sides of the house.
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
Revlimid [EMA] Revlimid as combination therapy with dexamethasone, or bortezomib and dexamethasone, or melphalan and prednisone is indicated for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for transplant.
	5.9.4 AACR - POUMON
AACR: Chi-Med, AstraZeneca's savolitinib helps some Tagrisso-resistant EGFR lung cancer patients [Fierce Pharma] The Chinese company Sunday rolled out phase 1b results showing that certain treatment-resistant patients showed improvement after receiving a combination of Tagrisso, which targets the EGFR gene mutation, and Chi-Med’s savolitinib, a MET inhibitor it’s developing with help from AZ.
AstraZeneca finds early-stage success with MET inhibitor in lung cancer [Biopharma Dive] The study focused on non-small cell lung cancer (NSCLC) patients who were previously treated with an EFGR-targeted therapy like Tagrisso and developed MET-driven resistance to such therapies.
Adding the MET Inhibitor Savolitinib to Osimertinib was Beneficial for Certain Pretreated Lung Cancer Patients in TATTON Trial [AACR] These are early-phase trials and the findings need confirmation in larger trials, Sequist noted.
	5.9.5 AACR - CAR-T
HER2-targeted CAR T-cell Therapy Safe, With Promising Antitumor Activity in Patients With Advanced Sarcoma [AACR] In this trial, Navai, Hegde, and colleagues treated 10 patients, ages 4 to 54, with refractory/metastatic HER2-positive sarcoma (five with osteosarcoma, three with rhabdomyosarcoma, and one each with Ewing sarcoma and synovial sarcoma).
Early studies hint at some potential for CAR-T therapy in solid tumors [Biopharma Dive] The research, conducted separately by investigators at Memorial Sloan Kettering (MSK) Cancer Center and Baylor College of Medicine, is notable because of the greater clinical challenges presented by solid tumors, which tend to be less susceptible to cancer cell therapy.
Mesothelin-targeted CAR T-cell Therapy Safe, Shows Early Promise in Patients With Advanced Solid Tumors [AACR] “If this approach is successful, 2 million patients with mesothelin-expressing solid tumors per year in the United States will be eligible for this treatment.”
	5.9.7 AACR - DIVERS
Use of Oral Contraceptives Protects Against Most-Fatal Types of Ovarian Cancer [Roswell Park] They looked at pooled data from 20 case-control studies involving 579 patients who died within 12 months of being diagnosed with ovarian cancer, matched to a control group of 2,279 patients who did not have ovarian cancer.
	5.9.9 AACR - IMMUNOTHÉRAPIES
Roche’s ipatasertib in combination with Tecentriq and chemotherapy shows promising anti-tumour activity in triple-negative breast cancer in early phase trial [Roche] Combination treatment demonstrated a confirmed objective response rate (ORR) of 73% (95% CI 53-88%), irrespective of tumour biomarker status.
AACR: Bristol-Myers Squibb's Opdivo-Yervoy duo provokes response in rare tumors [Fierce Pharma] Researchers have an idea as to why the BMS pairing only turned up a benefit in high-grade patients. “One preliminary hypothesis for this finding is that high-grade neuroendocrine carcinomas may have a higher tumor mutational burden, which is an indicator of better response to immunotherapy.”
Immune Checkpoint Inhibitor Combination Efficacious For Patients With High-grade Neuroendocrine Carcinoma [AACR] The aim of the Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART) trial is to evaluate the combinatorial efficacy of ipilimumab (1mg/kg every six weeks) and nivolumab (240mg every two weeks) in patients with rare tumor types.
The Parker Institute touts early results in pancreatic cancer trial — and a new model to accelerate drug development [STAT] “With the Parker Institute model, we have the opportunity to combine the scale and scope of a pharma trial with the science-driven approach of an investigator-initiated trial. It’s a more efficient way to get trials done,” said Vonderheide.
CRI-Sponsored Trial Reveals Promising Potential of Immunotherapy Combination in Metastatic Pancreatic Cancer [Cancer Research Institute] In this study, patients were treated with combinations of four different drugs, including two standard-of-care chemotherapies and two immunotherapies—one that inhibits the PD-1 immune checkpoint (nivolumab, BMS) and an experimental treatment that activates the CD40 pathway (APX005M, Apexigen).
	6.1 OBSERVATION
Asbestos exposure putting lives at risk 20 years since ban [IOSH] While it takes 20 years or more for exposure to lead to a cancer diagnosis, the Institution of Occupational Safety and Health (IOSH) is concerned that the number of buildings containing asbestos and a widespread lack of awareness and uncertainty on how to manage it – particularly among small and medium-sized organisations – means people will continue to become seriously ill in decades to come.
Asbestos still killing 5,000 Britons each year, 20 years after ban [The Telegraph] All this is preventable through good occupational safety and health. It is time for organisations to wake up and realise how dangerous asbestos is. There are no excuses."
	6.6 PUBLICATIONS
The value of a journal is the community it creates, not the papers it publishes [LSE Impact Blog] A different way of understanding journals is through the economics of clubs. Club economic models describe how a community can come together to produce goods that they couldn’t create individually, but from which all community members can benefit. Significantly they predict a number of characteristics for successful clubs.
Announcing a New AACR Journal : BLOOD CANCER DISCOVERY [AACR] Studies published in Blood Cancer Discovery will describe the mechanisms underlying tumorigenesis and disease biology; diagnostic and therapeutic development; and the translation of these data into the clinic.
Scientific integrity “a rare commodity these days:” Cancer journal makes its first retraction [Retraction Watch] JAMA Oncology has retracted a 2018 paper by a group from Sweden and the UK after the researchers discovered critical errors in their analysis that significantly altered the conclusions of the study.