Onco Actu du 19 décembre 2019

	1. BIOLOGIE
New study in mice points to why melanoma spreads — and perhaps how to prevent metastasis [STAT] His discovery might extend beyond melanoma. Lung and pancreatic tumor cells also use MCT1 to grab lactate from the bloodstream, presumably enabling those cancers, too, to metastasize.
CRI scientists discover metabolic feature that allows melanoma cells to spread [UT Southwestern Medical Center] In the study, published in Nature, melanomas growing in mice that were treated with an MCT1 inhibitor led to fewer melanoma cells in the blood and fewer metastatic tumors.
When cells cycle fast, cancer gets a jumpstart [Yale Cancer Center] “When a normal cell that divides quickly meets MLL-AF9, this combination creates a monster cell that is stuck in a state of perpetual fast division,” Guo said. “Their more slowly cycling counterparts remain normal and do not display the malignant cancer traits, even in the presence of cancer-causing mutations.”
	1.4 BIOLOGIE - TECHNOS, MODÈLES
Study finds widespread misinterpretation of gene expression data [Tel Aviv University] Importantly, the TAU researchers were able to show how the length bias they detected in many RNA-seq datasets led to the false identification of specific biological functions as cellular responses to the conditions tested.
	2.6 ETIOLOGIE - ENVIRONNEMENT
Roundup suit lawyer accused of $200 million extortion plot [CBS] Litzenburg threatened to find people who he would advise to sue the companies for exposing them to the chemical, according to the complaint. Litzenburg told the companies lawyers that he would cease searching for potential plantiffs in exchange for a multi-million-dollar consulting agreement, the complaint claims.
	3.1 PRÉVENTION - TABAC
WHO launches new report on global tobacco use trends [WHO] Number of males using tobacco globally on the decline, showing that government-led control efforts work to save lives, protect health, beat tobacco.
Tobacco epidemic at turning point as male smoking rates stall: WHO [Reuters] By 2020, the report said, there will be 10 million fewer tobacco users overall - male and female - than in 2018, and by 2025, that number will drop by another 27 million people.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
Special Report: FDA targets e-cigs that hook teens but don't help smokers quit [Reuters] E-cigarettes have been available in the United States since at least 2007, but the FDA did not formally get authority over the industry until nine years later, in 2016.
	3.2 PRÉVENTION - OBÉSITÉ
Weight loss linked to lower chance of getting breast cancer for women over 50 [NHS Choices] The Daily Telegraph and The Times both covered the study, with headlines suggesting that most or all women over 50 should lose weight. Neither made it clear that women of a healthy weight do not need to lose weight.
	4. DÉPISTAGE, DIAGNOSTIC ET PRONOSTIC
Gastric cancer susceptibility marker discovered [Institut Pasteur] Scientists demonstrated that gastric inflammatory lesions caused by H. pylori infection were more severe in a mouse model deficient in factor USF1. These results are also supported by clinical findings, since the prognosis is worse for gastric cancer patients with low levels of USF1 combined with low levels of p53.
	4.12 BIOPSIES LIQUIDES
Circulating Tumor DNA May Be Predictive of Disease Progression in Patients with Rectal Cancer [AACR] Forty-seven patients were evaluable for ctDNA and primary tumor response. Thirty-three percent of patients with poor tumor responses, as measured by tumor regression grade on magnetic resonance imaging, had detectable levels of ctDNA after chemoradiotherapy, compared to 5 percent of patients with good tumor responses.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
'Polygenic' profile could better predict disease risk for those with cancer mutations [Science] Genetic background strongly modifies impact of single gene mutations predisposing people to heart disease or cancer.
	4.3 DÉP., DIAG. & PRONO. - INDUSTRIELS
ArcherDX Announces Close of $55 Million Series C Financing [ArcherDx] Products Designed to Expand Adoption of Personalized Medicine by Enabling Health Care Providers to Deliver Actionable Genomic Information to Patients in Local Care Settings.
ArcherDX Raises $55M to Help Physicians Pick Best Cancer Therapies [Xconomy] Using molecular diagnostics, Myers says the company will be able to “push precision oncology into the early-stage setting” and improve patient care. “It’s a big year for us to prove we can do that,” he notes, adding that ArcherDX will initially target lung cancer.
FTC Challenges PacBio Acquisition, Says Illumina is a “Monopolist” [Xconomy] The debate in the UK over the Illumina-PacBio arrangement continues. Earlier this year, the UK’s Competition and Markets Authority (CMA) released provisional findings from its review, in which it posited that such a deal could “harm critically important innovation in the systems created to support DNA sequencing.”
FTC calls out Illumina as 'monopolist,' moves to block $1.2B acquisition of PacBio [EndPoints] The FTC’s five commissioners voted unanimously to challenge Illumina’s proposed takeover, setting an administrative trial for August 18, 2020, while moving to seek a temporary restraining order and preliminary injunction in federal court.
	4.5 DÉP., DIAG. & PRONO. - COLORECTAL
Recent Screening Rose among People under 50 after Release of New Colorectal Cancer Guidelines [ACS] Increase was unique to ages 45 to 49.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Bristol-Myers Squibb Announces Submission of Biologics License Application for CAR T-Cell Therapy Lisocabtagene Maraleucel (liso-cel) to FDA [BMS] BLA submission includes data from TRANSCEND NHL 001 trial evaluating liso-cel in patients with relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma.
	5.12.6 IMMUNOTHÉRAPIES - AMM
Merck's Keytruda nabs FDA panel's favor to line up for new bladder cancer OK [Fierce Pharma] The backing puts Keytruda on track to become the first in the PD-1/L1 class to nab an FDA approval in NMIBC by next January, ahead of rivals including Bristol-Myers Squibb’s Opdivo, Roche’s Tecentriq and AstraZeneca’s Imfinzi, all of which are also under test in similar NMIBC settings.
	5.12.7 IMMUNOTHÉRAPIES - VACCINS
First-in-human trial for new lung cancer immunotherapy [Cancer Research UK] The vaccine treatment will deliver cancer-associated antigens (MAGE A3 and NY-ESO-1) to antigen presenting cells called dendritic cells, causing the immune system to produce cytotoxic T cells, which target and kill cancerous cells expressing the antigens.
	5.2 PHARMA
After SABCS stunner, Seattle Genetics nabs FDA breakthrough tag for tucatinib [Fierce Biotech] The pivotal trial linked the tyrosine kinase inhibitor to reduced risk of progression and death in patients with and without brain metastases, leading Seattle Genetics CEO Clay Siegall to hail the data as “stunning.”
U.S. FDA Accepts and Grants Priority Review to sNDA for BRAFTOVI® (encorafenib) in Combination with ERBITUX® (cetuximab) (BRAFTOVI Doublet) for the Treatment of BRAFV600E-Mutant Metastatic Colorectal Cancer After Prior Therapy [Pfizer] As published in The New England Journal of Medicine (NEJM), results from the BEACON CRC trial showed improvements in overall survival (OS) and objective response rates (ORR) for both the BRAFTOVI Doublet and BRAFTOVI Triplet (BRAFTOVI, MEKTOVI and ERBITUX) combination, compared to ERBITUX plus irinotecan-containing regimens (Control).
	5.2.1 PHARMA - PARTENARIATS
Aduro stung as Novartis drops work on STING drug [Fierce Biotech] But the drug is not completely dead: Aduro said an ongoing phase 2 for ADU-S100 alongside Merck’s Keytruda as a first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma continues.
After taking a hard look at the data, Novartis punts Aduro’s STING drug — the latest in a long line of setbacks [EndPoints] ADU-S100 — which targets the STING pathway — will now be punted from Novartis’ portfolio, according to the biotech’s SEC filing, ending a combination trial with Novartis’ PD-1 spartalizumab (PDR001) as well as a study examining a combination of ADU-S100 with Yervoy for melanoma.
	5.2.2 PHARMA - FUSIONS & ACQUISITIONS
After being repeatedly jilted, this biotech was swept off its feet in a race to ASH: Inside Merck's $2.7B ArQule buyout [EndPoints] Merck’s negotiations began in earnest on June 27, as the final data on the ARQ 531 Phase I was on its way and the company had provided a small public snapshot: four partial responses out of six chronic lymphocytic leukemia patients who had become resistant or had not responded to earlier treatment.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
No OS benefit? No problem. FDA panel backs use of Lynparza in pancreatic cancer [EndPoints] Panelists voted 7-5 to recommend the drug for maintenance use in patients with germline BRCA-mutated metastatic adenocarcinoma of the pancreas, whose disease has not progressed on at least 16 weeks of first-line platinum-based chemotherapy.
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
European Commission approves Roche’s Kadcyla for the adjuvant treatment of people with HER2-positive early breast cancer with residual invasive disease after neoadjuvant treatment [Roche] Approval based on KATHERINE trial data showing Kadcyla cut the risk of disease recurrence or death by half compared to Herceptin in the adjuvant setting.
Seattle Genetics, Astellas snag quick FDA approval for bladder cancer-fighter Padcev [Fierce Pharma] A full course of Padcev cost between $110,000 to $120,000, Seattle Genetics estimates, with the final tally varying based on a patient’s weight and how long he or she stays on treatment.
Tox issues? Check. Questionable efficacy data? Check. OK to market? ODAC says check that box for Epizyme [EndPoints] Without much to choose from now, physicians like as many options as they can get on cancer. And for very sick patients, risks can be a secondary issue, even if 34% of tazemetostat patients had to suspend dosing due to toxicity.
FDA Grants Accelerated Approval to Astellas’ and Seattle Genetics’ PADCEV™ (enfortumab vedotin-ejfv) for People with Locally Advanced or Metastatic Urothelial Cancer, the Most Common Type of Bladder Cancer [Seattle Genetics] PADCEV is the First Treatment Approved for Locally Advanced or Metastatic Urothelial Cancer Following Treatment with Platinum-based Chemotherapy and a PD-1 or PD-L1 Inhibitor.
FDA approves new type of therapy to treat advanced urothelial cancer [FDA] “Padcev is an antibody-drug conjugate that targets Nectin-4, a cell surface protein expressed on bladder cancer cells and a cell-killing agent, monomethyl auristantin E.”
Backed by Yale Cancer Center research, FDA approves new drug for advanced bladder cancer [Yale Cancer Center] Persuasive data from the trial were presented last June at the American Society of Clinical Oncology (ASCO) annual meeting. Enfortumab vedotin, described by Petrylak as a “smart bomb”, is an antibody-drug conjugate, a type of therapy that combines an antibody that targets a specific protein on the surface of tumor cells with a payload of powerful chemotherapy.
	5.4 TRAITEMENTS - ECONOMIE
Low-cost breast cancer drug 'could save lives in low-income countries' [The Guardian] The medicine, made by a company called Samsung Bioepis, was assessed by WHO and found comparable to the original in terms of efficacy, safety and quality. That means it is eligible for procurement by United Nations agencies and for national tenders.
WHO prequalifies first biosimilar medicine to increase worldwide access to life-saving breast cancer treatment [WHO] The global average cost of trastuzumab from originator companies is $20 000, a price that puts it out of reach of many women and healthcare systems in most countries. The biosimilar version of trastuzumab is generally 65% cheaper than the originator. With this WHO listing, and more products expected in the prequalification pipeline, prices should decrease even further.
	5.9 AACR
2019 in Review: Progress Across Many Areas of Cancer Research [Cancer Research Catalyst] Here’s a look at some key developments in drug approvals, precision medicine, disparities research, and immunotherapy.
	6.1 OBSERVATION
Breast cancer survivors face other health risks after treatment [Reuters] “Non-cancer diseases, such as heart diseases, contribute to a significant number of deaths in patients with breast cancer, even higher than in the general population,” Al-Husseini told Reuters Health by email.
	6.10.1 POLITIQUES (USA)
Trump Administration takes historic steps to lower U.S. prescription drug prices [FDA] Proposed rule could allow certain prescription drugs to be imported from Canada; draft guidance explains how manufacturers could import drugs, biological products originally intended for sale in another country.
In a first step, Trump administration unveils two proposals to permit drug importation [STAT] “Our closed drug system doesn’t allow imports of unapproved foreign drugs for key historical reasons,” Gottlieb wrote. “We should not open up a side channel for foreign drugs.” Azar, who once held those same concerns, now insists drug importation can be done safely.
Top Republican blasts McConnell for derailing bipartisan drug pricing bill [STAT] The remarks are especially surprising from Grassley, one of the Senate’s highest-ranking Republicans. He told reporters at a briefing that his package has not gotten more Republican support “because McConnell has asked them not to [support it].”
Trump Administration Takes First Step to Allow Drug Imports From Canada [NY Times] The proposal is still a long way from being finalized, and many expensive drugs, like insulin, would be excluded from state plans.
Trump proposes rule for importing drugs from Canada; industry says it won't cut costs [Reuters] Industry trade groups in both countries opposed the plan, saying it will not lower costs and could hurt Canada’s drug supplies. Groups representing pharmaceutical and biotech companies called the proposal a political gesture.
	6.6 PUBLICATIONS
Universal Principled Review: A Community-Driven Method to Improve Peer Review [Cell] Despite being a staple of our science, the process of pre-publication peer review has few agreed-upon standards defining its goals or ideal execution. As a community of reviewers and authors, we assembled an evaluation format and associated specific standards for the process as we think it should be practiced.
Politics and Open Access [The Scholarly Kitchen] Let’s assume we now live in the post-apocalyptic world of a zero-embargo policy for federally funded research. What does this mean for the publishing of scholarly articles and their authors?
Science groups, senator warn Trump administration not to change publishing rules [Science] Letters blast rumored shift to immediate open access for taxpayer-funded studies.
	6.7.3 DMP
Can AI Fix Medical Records? [Nature] Digitized patient charts were supposed to revolutionize medical practice. Artificial intelligence could help unlock their potential.
	6.9 CONTROVERSES
Embattled cancer researcher loses legal bid to be reinstated as department chair at OSU [Retraction Watch] Croce, who earns more than $800,000 per year from OSU, has had nine papers retracted, and more than a dozen have been subjected to a correction or an expression of concern.