Onco Actu du 19 juin 2018

	1. Biologie
Ovarian cancer cells switched off by 'unusual' mechanism [Imperial College] When AXL becomes activated, it renders cancer cells more aggressive, increasing their ability to move and spread to other parts of the body. However, it also reveals itself to OPCML, which then drags the bound molecules into a specific region of the cell where AXL is deactivated.
Study Suggests Well-Known Growth Suppressor Actually Fuels Lethal Brain Cancers [Cincinatti Children's] “Our study uses analysis of The Cancer Genome Atlas to show that AMPK proteins are highly expressed in lethal human glioblastoma, that inhibiting AMPK by genetic means shrinks brain tumors and prolongs survival in mice. It also shows that deleting AMPK from the whole body of adult mice is safe for the animals.”
Genomics offers new treatment options for infants with range of soft tissue tumours [Sanger Institute] Scientists studied historic tumours from Great Ormond Street Hospital's archives and uncovered the genetic changes causing a group of related infant cancers.
	3.3 Prévention - Vaccins
New Gardasil ad campaign gets it (mostly) right. It shouldn’t have taken a decade [STAT] The Versed effort helps debunk two common misperceptions that Merck’s earlier campaign had stoked: that Gardasil is a female-specific vaccine for cervical cancer, and that sexual transmission isn’t important, or at least isn’t worth talking about.
	4.1 Dép., diag. & prono. - Prostate
Wales 'behind' in technology to detect prostate cancer [BBC News] The Multiparametic MRI (mpMRI) scan, which is done before a biopsy, is able to boost detection of prostate cancer. In England, an NHS trial is under way to cut prostate cancer diagnosis times from six weeks to a matter of days using the scan. But in Wales only three out of seven Welsh health boards provide the scan, as it is not currently recommended by the National Institute of Clinical Excellence (NICE).
	4.10 Dép., diag. & prono. - FDA, EMA, NICE,...
Myriad's BRACAnalysis CDx® Supplementary PMA Accepted by FDA for Review as a Companion Diagnostic for Talazoparib in Metastatic Breast Cancer [Myriad] Myriad's sPMA and Pfizer's NDA submissions are based on results from the Pfizer-sponsored EMBRACA trial, which evaluated talazoparib versus chemotherapy in patients with germline (inherited) BRCA-mutated (gBRCAm), HER2-negative locally advanced or metastatic breast cancer (MBC). The primary results of the study were presented at the San Antonio Breast Cancer Symposium in December 2017.
	5. Traitements
JAK Inhibitors Associated with Aggressive Lymphoma [ASH] Though not a cure, JAK inhibitors are very effective at providing symptom relief, said study coauthor Heinz Gisslinger, MD, of the Medical University of Vienna in Austria. “However, we started noticing sporadic cases of lymphomas developing in patients being treated for myeloproliferative neoplasms and wanted to know if this phenomenon was connected to treatment.”
Biosimilars for Cancer Emerge as Patents on Widely Used Biological Drugs Expire [NCI] “The fact that biosimilars have been used in Europe and in Japan should give us some assurance that the drugs are as safe and effective as the corresponding reference products.”
	5.12 Immunothérapies
How many PD-1 and PD-L1 checkpoint inhibitors do we need? [Pipeline Review] Analysis of the PD-1 and PD-L1 checkpoint inhibitor pipeline revealed 41 unique molecules in clinical development by pharmaceutical companies, of which 12% are bispecific molecules and 27% are only developed so far in less regulated countries. Further 15 unique molecules are undergoing IND-enabling studies or have already applied for clinical trial of which 40% are bispecific molecules.
	5.12.2 Immunothérapies - CAR-T, thérapies cellulaires
FDA hits Ziopharm CAR-T trial with clinical hold [FierceBiotech] Shares in Ziopharm fell 12% in premarket trading following the release of the news. The drop reflects the readthrough from the hold for the prospects of a technology that is central to Ziopharm’s plans.
Ziopharm Oncology Reports on Status of Investigational New Drug Application for Phase 1 Trial to Evaluate CD19-targeted CAR T Therapy [Ziopharm] Ziopharm believes this feedback from the FDA does not affect timelines for the Company’s planned trial at the National Cancer Institute using the Sleeping Beauty platform to target solid tumors infusing TCR-modified T cells. The second-generation clinical trial evaluating Sleeping Beauty-manufactured CD19-specific CAR-T cells continues enrolling and infusing patients at MD Anderson.
	5.12.5 Immunothérapies - Pharma
CAR-T startup Allogene Therapeutics picks up veteran analyst Eric Schmidt as CFO [STAT] The goal at Allogene is to develop a suite of off-the-shelf CAR-T therapies that do not need to be personalized for each cancer patient. The startup raised $300 million in private funding right out of the gate, some of it from Belldegrun’s venture capital firm.
	5.12.8 Immunothérapies - Economie
Johns Hopkins spinout WindMIL grabs $32.5M to fuel its work on a next-gen approach to cell therapy [EndPoints] The Baltimore-based startup is tapping memory T cells residing in the bone marrow — and their innate ability to recognize tumors — to make what they call a novel class of cancer therapy.
	5.2.2 Pharma - Fusions & Acquisitions
Roche bags full ownership of Foundation Medicine in $2.4B follow-up buyout [EndPoints] While Foundation Medicine does have an FDA-approved diagnostic called FoundationOne CDx, Roche is choosing to highlight its broader potential in comprehensive genomic profiling of cancers, which can both guide development of treatments and match patients with the appropriate therapies.
Roche pays $2.4 billion for rest of cancer expert Foundation Medicine [Reuters] It is the latest in a series of bolt-on acquisitions by Roche as the world’s largest marker of cancer drugs seeks to tap into promising technology developed by biotech companies to drive future growth as its older drugs face competition. Earlier this year it agreed to buy the rest of U.S. cancer data company Flatiron Health for $1.9 billion in a similar deal.
Roche and Foundation Medicine reach definitive merger agreement to accelerate broad availability of comprehensive genomic profiling in oncology [Roche] Merger focuses on driving ubiquity of Foundation Medicine’s high quality comprehensive genomic profiling (CGP) testing and innovative data services to realise Roche’s vision of personalised healthcare.
	5.3 Traitements - FDA, EMA, NICE...
Budget Matters: Infrastructure to Support Robust Generic Drug Competition [FDA] The first initiative will create a new review platform — the Knowledge-aided Assessment & Structured Application (KASA) platform — to modernize generic drug review from a text-based to a data-based assessment.
	5.9.3 EHA
Bristol-Myers, AbbVie eye new use for myeloma drug Empliciti after phase 2 combo win [FiercePharma] Now, Bristol-Myers and AbbVie will take the results to health authorities in search of a new Empliciti use. Right now, the drug is approved alongside Celgene’s Revlimid and dexamethasone for patients who have already received anywhere from one to three prior treatments.
AbbVie unveils high undetectable disease rates for venetoclax/rituximab combo [PharmaTimes] According to a new subgroup analysis from the pivotal Phase III MURANO trial, 83 percent of patients given the combination maintained undetectable minimal residual disease (uMRD) and were progression-free at 13.8 months of follow-up.
Daiichi says it’s ready to change the standard of care for acute myeloid leukemia — but it’s a work in progress [EndPoints] The results are statistically significant but unspectacular, with 27% of the patients suffering from treatment-resistant acute myeloid leukemia with FLT3-ITD mutations in the drug arm making it to 52 weeks compared to 20% of the chemo patients in the control arm.
Phase 3 QuANTUM-R Study Demonstrates Daiichi Sankyo’s Quizartinib Significantly Prolongs Overall Survival as Single Agent Compared to Chemotherapy in Patients with Relapsed/Refractory AML with FLT3-ITD Mutations [Daiichi-Sankayo] The estimated survival probability at 1 year was 27 percent for patients who received quizartinib and 20 percent for patients who received salvage chemotherapy.
	6.10 Politiques
NHS funding: New money for England is a start, but it must be spent wisely [Cancer Research UK] And crucially, it’s only being provided to NHS England, which funds hospitals, GPs practices, and other healthcare services. The new cash boost won’t apply to the organisations providing our medical education, public health, social care, or vital government-funded medical research.
	6.5 Médecines alternatives
ASCO endorses the integration of quackery into breast cancer care [Science-based Medicine] In 2014, the Society for Integrative Oncology first published clinical guidelines for the care of breast cancer patients. Not surprisingly, SIO advocated “integrating” dubious therapies with oncology. Last week, the most influential oncology society, the American Society of Clinical Oncology (ASCO), endorsed a 2017 update to the SIO guidelines, thus endorsing the “integration” of quackery with oncology and paving the way for insurance coverage.
	6.9 Controverses
Why the Medical Research Grant System Could Be Costing Us Great Ideas [NY Times] Funding is harder to find in general, and the current approach favors low-risk research and proposals by older scientists and white men.