Onco Actu du 24 février 2020

	1. BIOLOGIE
Researchers Discover Stem Cells That May Drive Aggressive Behavior in Glioblastoma [Memorial Sloan Kettering Cancer Center] “Radial glia cells previously were not thought to persist in adulthood,” Dr. Tabar explains. “If glioblastoma tumors arise from them, that may mean that humans retain some radial glia cells in our brains as adults."
Tension in tumour cells keeps metabolism high [Nature] Tumours are often stiffer than normal tissues and show abnormally fast metabolism of glucose. It emerges that the link between these two traits involves tension in a network of protein filaments in cells.
	1.1 BIOLOGIE - GÉNOME
Zooming in on breast cancer reveals how mutations shape the tumour landscape [Cancer Research UK] An international team of scientists*, brought together by an ambitious £20 million Grand Challenge award from Cancer Research UK, has developed intricate maps of breast tumour samples, with a resolution smaller than a single cell.
Fight against endometrial cancer boosted with new molecular road map [WUSTL] Funded by the National Cancer Institute, the study also suggests a potential role for already approved drugs that target proteins newly implicated in this disease also commonly known as uterine cancer.
Multi-Omic Endometrial Cancer Study Reveals Novel Pathways, Treatment Targets [Genome Web] In a study published in Cell on Thursday, the researchers described their characterization of 95 prospectively collected endometrial carcinomas and 49 normal tissues, comprising 83 endometrioid and 12 serous tumors.
Loss of p53 protein strikes a nerve to aid tumour growth [Nature] Tumours often grow entangled among neurons, which makes the cancer difficult to treat. The finding that cancer cells hijack neighbouring neurons to promote tumour growth suggests new therapeutic targets.
	1.1.2 BIOLOGIE - GÉNOME - PAN CANCER
Pan-Cancer Analysis Points to Possible Functional Effects of Passenger Mutations [Genome Web] With the help of a functionally informative sequencing method called FunSeq2, the researchers identified non-driver, somatic mutations and their predicted functional impact in 2,548 tumors profiled for the Pan Cancer Analysis of Whole Genomes (PCAWG).
Scientists find many gene ‘drivers’ of cancer, but warn: Don’t ignore ‘passengers’ [Yale] In the paper in Cell, they report on experiments intended to show whether passenger mutations could help explain the 10% of cancer cases in which researchers found few or no clear genetic drivers.
A Global Look at Cancer Genomes [NIH Director's Blog] The challenging next steps include connecting the cancer genome data to treatments and building meaningful predictors of patient outcomes.
Genetics and evolution in cancer [Science-Based Medicine] Unfortunately, what this study also shows is that, thanks to evolution, curing a given cancer is just not going to be as simple as getting a biopsy of a tumor and picking a targeted agent or two to blast the tumor into oblivion.
	1.2 BIOLOGIE - BIOBANQUES
The making of a living ovarian cancer biobank [Cancer Research UK] Since the biobank has been established, the team have analysed the ovarian cancer cells living and dividing in acute detail. And what they have uncovered is a remarkable level of differences between ovarian cancers, with no two cancers genetically looking the same.
	1.4 BIOLOGIE - TECHNOS, MODÈLES
Scientists turn organs transparent — and use a new technique to capture 3D pictures of what’s inside [STAT] The new work involved a three-pronged approach: stripping the pigment and fats from organs; capturing images of entire organs with a specially designed, larger microscope; and developing an algorithms to analyze those images and spit out maps labeled with specific cellular structures.
Translating preclinical models to humans [Science] Instead of attempting to “humanize” animal experimental models, which is possible to only a limited extent, greater success may be obtained by humanizing computational models derived from animal experiments.
Intratumoral heterogeneity may be responsible for chemotherapy resistance in patients with small cell lung cancer [MD Anderson Cancer Center] To overcome the lack of recurrent SCLC samples, the team developed novel disease models by isolating circulating tumor cells (CTCs) from a simple blood draw. The cells, placed under the mouse’s skin, develop tumors representative of the patient from whom they were derived.
New technique allows scientists to 'listen in' on cancer cells [Cancer Research UK] This is the first time that scientists have been able to analyse many different signalling molecules at once in individual cells within replicas of patients’ tumours.
	2.5 ETIOLOGIE - GÉNOME
Endometrial Cancer Study Identifies 24 Variants Linked to Disease Predisposition [Genome Web] In a study published in the Journal of Medical Genetics, the researchers reported that they identified SNPs in HNF1B, KLF, EIF2AK, CYP19A1, SOX4, and MYC, which are all genes involved in cell survival, estrogen metabolism, and transcriptional control.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
Journal retracts hotly contested paper on vaping and heart attacks [Retraction Watch] Brad Rodu, a professor at the University of Louisville who comments frequently on vaping, asked the journal to retract the study shortly after it was published. The study, he said, had failed to account for which happened first — heart attacks or vaping.
The great vape debate: are e-cigarettes saving smokers or creating new addicts? [The Guardian] The US is cracking down on vaping while the UK is promoting e-cigarettes as an aid to giving up smoking. Where does the truth lie?
Are e-cigarette companies helping smokers quit? Survey suggests Americans don’t buy it [STAT] Some 59% of Americans said they do not believe the industry is working to “be part of the solution to reduce the health effects of smoking,” in a survey of 1,200 people conducted by the Truth Initiative and shared exclusively with STAT.
Teen vaping is bad. Nicotine makes it worse, says researcher [Science] Animal studies hint at long-term harm to the developing brain.
How Juul gets kids addicted to vaping: it's even worse than you think [The Guardian] Massachusetts is suing the e-cigarette company for its predatory ads to children. Hopefully other states will follow suit.
	3.3 PRÉVENTION - VACCINS
HPV Vaccine Hesitancy [ESMO] It is estimated that the HPV vaccine crisis result to date in around 5000 deaths from cervical cancer in Japan. Many of these deaths could still be prevented if vaccination coverage with extended catch-up can be rapidly restored.
	3.4 CHIMIOPRÉVENTION
Research suggests statins could lower ovarian cancer risk [Cancer Research UK] While the study suggests that statins could lower ovarian cancer risk, more research needs to be done specifically looking at their use and impact on women’s risk of developing the disease.
	4.12 BIOPSIES LIQUIDES
Examining Diverse Uses for Liquid Biopsies [Cancer Research Catalyst] Ongoing research into the uses of liquid biopsy were presented at the AACR Special Conference on Advances in Liquid Biopsies, held last month in Miami. Here, we highlight five studies presented at the meeting that demonstrate the diverse uses for liquid biopsy.
GRAIL Initiates First Interventional Study Using its Multi-Cancer Early Detection Test to Guide Clinical Care [Grail] A prospective, multi-center study, PATHFINDER marks the first time GRAIL’s test results will be returned to healthcare providers and communicated to participants to help guide appropriate diagnostic workup for more than 50 cancer types.
	4.15 DÉP., DIAG. & PRONO. - IMAGERIE
Using oxygen to make cancer visible [DKFZ] Scientists from the German Cancer Research Center have developed a new method that uses oxygen to identify brain tumors more effectively by magnetic resonance tomography (MRT). To do so, they rely on a metabolic feature of the tumor cells that they can make visible using a completely new imaging method.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
Cancer, Pathology Organizations Developing Clinical Guidelines for MMR, MSI Testing [Genome Web] "This guideline is the first to address testing based more on the methodology status of a biomarker and less on the cancer type or tumor origin," guideline developer and pathologist Russell Broaddus said in a statement.
Your DNA is a valuable asset, so why give it to ancestry websites for free? [The Guardian] DNA testing companies are starting to profit from selling our data on to big pharma. Perhaps they should be paying us.
	5. TRAITEMENTS
Chemotherapy For Cancer Treatment Could Soon Be Unviable Because Of Antibiotic-Resistant Superbugs, Doctors Fear [Newsweek] Of the 100 oncologists in the U.K. surveyed between December 20, 2019 and February 3, 2020 by the Longitude Prize—which was established to help tackle antimicrobial resistance—95 percent said they were worried about the effect superbugs could have on their patients.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
Researchers implicate gene in DNA errors in aggressive breast cancer [UNC] Researchers led by UNC Lineberger Comprehensive Cancer Center’s Gaorav Gupta, MD, PhD, described the role of a mutation in the Mre11 gene in triple negative breast cancer and how a disruption of Mre11 function plays a significant role in the genomic instability of that cancer type.
Scientists identify drug fragments that could lead to new cancer drugs [Institute of Cancer Research] In a new study, published in the journal Scientific Reports, researchers at The Institute of Cancer Research, London, took a systematic approach to look at the enzyme tankyrase.
Combination Drug Therapy For Childhood Brain Tumors Shows Promise In Laboratory Models [Johns Hopkins] In experiments with human cells and mice, researchers at the Johns Hopkins Kimmel Cancer Center report evidence that combining the experimental cancer medication TAK228 (also called sapanisertib) with an existing anti-cancer drug called trametinib may be more effective than either drug alone in decreasing the growth of pediatric low-grade gliomas.
	5.12.1.1 IMMUNOTHÉRAPIES - PARTENARIATS - IMMATICS
GSK pays $50M for 2 solid tumor cell therapies from Immatics [Fierce Biotech] Germany’s Immatics has entered into a series of collaborations in recent years, leveraging its pool of around 200 targets to land deals with Amgen, Celgene and Genmab.
GSK taps Immatics' cell therapy science in research deal [Biopharma Dive] GSK will pay Immatics about $50 million upfront to gain access to the first two programs, which will be based around the smaller company's work on T cell receptor therapies.
TCR-focused Immatics adds another marquee name to its list of partners: GSK [EndPoints] Unlike CAR-T cells that can recognize abnormal proteins expressed on the surface, TCRs can recognize tumor-specific proteins inside cells. That makes CAR-T therapies more amenable to blood cancers, while TCR therapies-in-development have potential across multiple tumor types.
	5.12.1.2 IMMUNOTHÉRAPIES - PARTENARIATS - CELLECTIS
Cellectis and Servier Expand Collaboration on UCART19 Products [Cellectis] Cellectis grants additional rights to Servier to develop and commercialize all next generation gene-edited allogeneic CAR T-cell products targeting CD19, including ALLO-501A.
Cellectis boosts its coffers in revised off-the-shelf CAR-T deal with Servier [EndPoints] Cellectis handed the global license to develop and sell all next-generation gene-edited allogeneic CAR T-cell candidates targeting CD19 to Servier. Meanwhile, Cellectis is set to regain exclusive control over the five undisclosed allogeneic CAR-T cell targets previously covered by the initial Servier agreement.
	5.12.11 IMMUNOTHÉRAPIES - PRÉ-CLINIQUE
What’s Next in Immunotherapy for Pancreatic Cancer? New Immune Cell Type May Be Key [Memorial Sloan Kettering Cancer Center] The researchers showed that activating innate lymphoid cells with drugs mobilizes T cells to shrink pancreatic cancer tumors. This could be an important step, as pancreatic cancers have not responded to checkpoint inhibitor drugs.
	5.12.13 IMMUNOTHÉRAPIES - BIOMARQUEURS
Osteosarcoma profiling reveals why immunotherapy remains ineffective [MD Anderson Cancer Center] The study, published in Nature Communications, found that poor infiltration of the tumor by immune cells, low activity from available T cells, a lack of immune-stimulating neoantigens, and multiple immune-suppressing pathways all combine to dampen responses to immunotherapy.
Study shows long-term survival benefit for certain patients with advanced lung cancer [EurekAlert!] According to the results of a large, global study led by Yale Cancer Center researchers, even a tiny amount of a biomarker known as PD-L1 (programmed death-ligand1) can predict a long-term survival benefit from using pembrolizumab (Keytruda).
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Controlling CAR T Cells with Light Selectively Destroys Skin Tumors in Mice [UCSD] In tests in mice, administering the engineered CAR T cells and stimulating the skin tumor sites with blue LED light reduced tumor size by eight to ninefold. The results were observed in nine out of ten mice tested. Engineered CAR T cells on their own did not inhibit tumor growth.
New study finds cellular immunotherapy treatment associated with improved quality of life [ASH] Adult cancer patients reported better physical and social function after undergoing CAR-T therapy.
Remodeled CAR T-Cell Therapy Reduces Side Effects in First Clinical Trial [NCI] In 2017, NCI researchers tweaked their original CAR T-cell design with the goal of creating a safer and more effective therapy. Now results from the first clinical trial of the remodeled CAR T cells suggest that they may have achieved part of their goal.
Carl June on CRISPR, CAR–T and how the Vietnam War dropped him into medicine [EndPoints] Endpoints caught up with June about the long road both he and the field took to get here, if the treatment will ever scale up, and where CRISPR and other advancements can lead it.
	5.12.3 IMMUNOTHÉRAPIES-COMBINAISONS
Bristol-Myers shrugs off another Opdivo combo flop as $1.74B deal goes pfffft [EndPoints] The big idea here was that inhibiting CSF1R would reduce the number of immunosuppressive tumor-associated macrophages in the tumor microenvironment, lending Opdivo a hand to accomplish its task in a broader range of patients. But it didn’t pan out here.
Five Prime, Bristol Pancreatic Cancer Drug Combo Fails Phase 2 Test [Xconomy] The South San Francisco-based biotech said BMS, which acquired rights to cabiralizumab as part of the deal inked in 2015, has no plans to sponsor additional development of the investigational drug.
Five Prime Therapeutics Provides Update on Phase 2 Trial of Cabiralizumab Combined with Opdivo® in Pancreatic Cancer [Five Prime] Phase 2 Trial of Cabiralizumab plus Opdivo (nivolumab) with and without Chemotherapy in Advanced Pancreatic Cancer Did not Meet Primary Endpoint.
	5.12.5 IMMUNOTHÉRAPIES - PHARMA
FDA grants priority review to Roche’s Tecentriq monotherapy as first-line treatment of certain people with advanced non-small cell lung cancer [Roche] This sBLA is based on results from the Phase III IMpower110 study, which showed that Tecentriq monotherapy improved overall survival (OS) by 7.1 months compared with chemotherapy (median OS=20.2 versus 13.1 months; hazard ratio [HR]=0.595, 95% CI: 0.398–0.890; p=0.0106) in people with high PD-L1 expression (TC3/IC3-WT).
Merck Receives Complete Response Letter from the US FDA for Supplemental Biologics License Applications (sBLAs) for KEYTRUDA® (pembrolizumab) Six-Week Dosing Schedule [Merck] Merck is reviewing the letter and will discuss next steps with the FDA.
FDA Rejects Merck's 6-Week Dosing Schedule for Keytruda [Biospace] It doesn’t happen that often, but Merck’s checkpoint inhibitor Keytruda (pembrolizumab) received a rejection from the U.S. Food and Drug Administration (FDA). Six all at once, as a matter of fact.
	5.16 TRAITEMENTS - CHIRURGIE
Breast cancer surgery: better results with higher case numbers [Iqwig] Increased chances of survival and fewer follow-up operations – positive correlation between volume and quality in the surgical treatment of breast cancer.
	5.2 PHARMA
AstraZeneca cans cancer pipeline efforts [Fierce Biotech] The two axed drugs are both aimed at cancer targets: The first is MEDI7247, an anti-ASCT2 antibody-drug conjugate, and an oleclumab plus AZD4635 CD73 and A2A inhibitor combo.
Astellas and Seattle Genetics Receive FDA Breakthrough Therapy Designation for PADCEV™ (enfortumab vedotin-ejfv) in Combination with Pembrolizumab in First-Line Advanced Bladder Cancer [Astellas] Breakthrough Therapy Designation Based on Initial Results from Phase 1b/2 EV-103 Clinical Trial.
	5.2.3 PHARMA - ÉCONOMIE
‘The disruption is enormous.’ Coronavirus epidemic snarls science worldwide [Science] An estimated 80% of all active pharmaceutical ingredients (APIs)—the raw materials for drugs—are produced in China and India, according to recent testimony by Rosemarie Gibson, author of China Rx, before the United States-China Economic and Security Review Commission in Washington, D.C. They include the compounds used to treat everything from bacterial infections and cancer to heart disease and diabetes.
	5.2.6 PHARMA - BIOTECH
After digging through discards, biotech startup is making a $45M bet it can fix a failed cancer therapy [EndPoints] They are enrolling patients with a wide range of solid tumors to the Phase Ib dose escalation trial — from pancreatic adenocarcinoma and ovarian cancer to prostate cancer and triple negative breast cancer — as naptumomab targets the oncofetal antigen 5T4.
PharmaMar, Jazz get FDA priority review for lung cancer drug [Fierce Biotech] The FDA’s acceptance of lurbinectedin for priority review reflects the unmet medical need in SCLC. While the FDA has approved Bristol-Myers Squibb’s Opdivo and Merck’s Keytruda for third-line use in recent years, the options available to second-line patients have remained unchanged.
	5.3 TRAITEMENTS - FDA, EMA,...
Restrictions in use of cyproterone due to meningioma risk [EMA] The medicines should only be used for reduction of sex drive in sexual deviations in men when other treatment options are not suitable. There is no change in use of the medicines in men for prostate cancer.
	5.4 TRAITEMENTS - ECONOMIE
Kidney cancer drug gets initial ‘no’ for the NHS in England [Cancer Research UK] The National Institute for Health and Care Excellence (NICE) has made an initial decision not to recommend pembrolizumab (Keytruda) and axitinib (Inlyta) for advanced renal cell cancer.
	5.5 ASCO
Dean’s Digest – ASCO GU 2020 [OBR] Blood based cancer component assessments, termed “liquid biopsies” were much in vogue throughout ASCO GU 2010. Liquid biopsies include identification of intact circulating tumor cells, tumor specific cell free DNA mutations, copy number variants, methylation signatures, transcriptomics, micro RNA signatures, exosomes, microvesicles as well as tumor-educated platelets.
	5.5.14 ASCO (VESSIE)
New Astellas, Seattle Genetics Padcev combo data spark $5.8B sales hopes [Fierce Pharma] At the 11.5 month-mark of a phase 1b/2 study, the pairing had provoked a response in 73.3% of patients ineligible for cisplatin chemo, the companies said in a Friday morning presentation at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium.
	5.5.19 ASCO (REIN)
Opdivo (nivolumab) Plus Yervoy (ipilimumab) Demonstrates Continued Survival Benefit at 42-Month Follow-up in Patients with Previously Untreated Advanced or Metastatic Renal Cell Carcinoma [BMS] Results represent the longest follow-up with any immuno-oncology–based therapy in this setting.
Updated CheckMate -025 Results Show 26% of Patients Treated with Opdivo are Alive at Five Years in Patients with Previously Treated Advanced or Metastatic Renal Cell Carcinoma [BMS] With an extended minimum follow-up of 64 months, patients treated with Opdivo continue to demonstrate OS benefit with 26% of patients alive compared to 18% of patients treated with everolimus.
BMS leans on new long-term Opdivo data in crowded kidney cancer field [Fierce Pharma] More than half—56%—of patients treated with the pairing were alive at the 42-month mark, compared with 47% of those taking Pfizer’s Sutent, the New Jersey drugmaker showed over the weekend at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium.
Novel targeted drug shows promise in advanced kidney cancer [Dana-Farber Cancer Institute] Researchers from Dana-Farber Cancer Institute report a response rate of 24 percent across all risk categories of patients given an oral first-in-class agent that targets hypoxia-inducible factor (HIF) 2-a, which promotes new blood vessel growth that fuels kidney tumors.
	5.5.3 ASCO (PROSTATE)
Real-World Study of 6,000+ Medicare Patients with Advanced Prostate Cancer Shows Adding PROVENGE® (sipuleucel-T) to Treatment Regimen Reduced Risk of Death by 45% [Dendreon] – New Data Presented at ASCO Genitourinary Cancers Symposium Finds Adding PROVENGE to Commonly Prescribed Oral Therapies Extends Median Survival by 14.5 Months.
	6. LUTTE CONTRE LES CANCERS
First baby is born through new egg-freezing technique [The Guardian] Cancer patient’s immature eggs were collected, matured in lab and frozen for use five years on.
First baby born to cancer patient from eggs matured in the lab and frozen [Annals of Oncology Press Release] Fertility doctors in France have announced the birth of the first baby to be born to a cancer patient from an immature egg that was matured in the laboratory, frozen, then thawed and fertilised five years later.
	6.1 OBSERVATION
The Lancet Oncology: Young cancer survivors face higher risk of severe health problems in later life than the general population, study suggests [EurekAlert!] Cancer survivors who are diagnosed during adolescence or early adulthood (age 15-20 years) are at increased risk of premature death compared to the general population.
Drop in cancer deaths reflect failures of our society. Really [Boston Globe] When deaths due to poverty, obesity, addiction, and depression rise, cancer death rates automatically fall, because the two categories of death share risk factors.
	6.10 POLITIQUES
Joint Statement I Prevention at the heart of Europe’s Beating Cancer Plan [EPHA] Europe’s Beating Cancer Plan needs a thorough prevention pillar to tackle challenges common to all non-communicable diseases (NCDs), reads a statement by 30+ health organisations.
	6.10.1 POLITIQUES (USA)
FDA calls states’ bluffs on drug importation [STAT] Importation has never been about actually bringing drugs into the U.S. — it’s about bringing their prices here.
If you were a cancer patient, where would you rather be — the United States or Europe? [EndPoints] Frustrated by the lack of legislation implemented to lower soaring drug prices in the United States — a key issue that has elicited outrage across both ends of the political spectrum — the White House recently issued a report suggesting that US drug prices aren’t unreasonable, it’s that developed nations aren’t paying their fair share.
	6.11 PATIENTS
Comparative twin study: Access to healthcare services in the NHS and the American private insurance system [BMJ] We are identical twins, both having been treated for breast cancer within the past five years. Nora, a London-based university professor, received her care through the NHS; Nancy, a US government employee (with what is considered in the US an excellent employer insurance plan), was treated in the US.
Boehringer Ingelheim Launches Patient-Centric MyStudyWindow Powered by Carebox [Boehringer Ingelheim] Boehringer Ingelheim offers MyStudyWindow to provide patients, families, caregivers, and doctors consistent access to information about Boehringer Ingelheim’s actively recruiting studies conducted at global site locations.
	6.6 PUBLICATIONS, POLITIQUES SCIENTIFIQUES
Reforming Research Assessment: A Tough Nut to Crack [The Scholarly Kitchen] The real question about TOP Factor – and any other attempt to reform research culture – is whether anyone who matters (promotion and tenure committees, funding agencies, etc.) will care about or use it. The lesson of past attempts is that this is an incredibly tough nut to crack.
	6.7.1 IA/BIOINFORMATIQUE
The EU just released weakened guidelines for regulating artificial intelligence [MIT Technology Review] The new criteria are much weaker than the ones suggested in a version of the white paper leaked in January.
Europe plans to strictly regulate high-risk AI technology [Science] The commission will draft new laws—including a ban on “black box” AI systems that humans can’t interpret—to govern high-risk uses of the technology, such as in medical devices and self-driving cars.
	6.9 CONTROVERSES
Responses to “The Cancer Industry: Hype vs. Reality” [Scientific American] Readers critique a journalist’s critique of cancer medicine.