Onco Actu du 18 avril 2019

	1. BIOLOGIE
U of T researchers ‘reverse engineer’ brain cancer cells to find new targets for treatment [University of Toronto] Taking 10 unique patient-derived glioblastoma stem cell cultures collected by the Dirks research team, the Angers lab used CRISPR “cell fitness screens” to determine which genes in the cancer stem cells were required for the cells to survive and to grow – and were therefore important for tumour progression.
New study targets Achilles’ heel of pancreatic cancer, with promising results [Salk] The findings, published in Nature on April 17, 2019, show that pancreatic stellate cells—resident cells typically dormant in normal tissue—become activated and secrete proteins to form a shell around the tumor in an attempt to wall off and contain it.
	1.4 BIOLOGIE - TECHNOS
CRISPR edits lung-disease gene in utero, hitting only the affected organ in a mouse study [STAT] One crucial difference between people and mice would make editing SFTPC in human fetuses more difficult, however. People, unlike mice, need that gene, so CRISPR would have to repair it, not delete it, a much stiffer challenge.
Powerful CRISPR cousin accidentally mutates RNA while editing DNA target [Science] Off-target editing could complicate developing safe “base-edited” therapies.
	4.1 DÉP., DIAG. & PRONO. - PROSTATE
Artificial intelligence performs as well as experienced radiologists in detecting prostate cancer [UCLA] In tests, FocalNet was 80.5 percent accurate in reading MRIs, while radiologists with at least 10 years of experience were 83.9 percent accurate.
	4.12 BIOPSIES LIQUIDES
Natera's Liquid Biopsy Exome Could Enable Recurrence Monitoring Without Tissue Samples [Genome Web] So far, Natera has not published any data on the accuracy of the method, its limits of detection, or reproducibility across different cancer types or stages, so a variety of questions remain as to its limitations and how it might compare to existing panel-based liquid biopsy tests used for therapy selection.
Breast cancer blood test could help to spot relapse earlier [Imperial College] In a small study, carried out by the University of Leicester and Imperial College London and funded by Cancer Research UK, researchers showed that the blood test was able to detect 89 per cent of all relapses, on average 8.9 months quicker than imaging.
	4.3 DÉP., DIAG. & PRONO. - INDUSTRIELS
Agilent Receives an Expanded FDA Approval for its Companion Diagnostic in NSCLC [Agilent] PD-L1 IHC 22C3 pharmDx Can Now Be Used to Identify a Broader Range of NSCLC Patients for First-line Treatment With KEYTRUDA® (pembrolizumab).
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
Triple negative breast cancers can adopt reversible state that is resistant to chemotherapy [MD Anderson Cancer Center] Hoping to find new treatment targets for resistant TNBC, the researchers discovered that these cells had become dependent on oxidative phosphorylation for energy production. This pathway is the target of IACS-10759, the first-small molecular discovered and developed by MD Anderson’s Therapeutics Discovery division.
Three Colorado studies show how tumors hijack the immune system to resist radiation therapy [University of Colorado] What is driving this resistance to radiotherapy? In a new study published in the Journal of the National Cancer Institute, Karam and colleagues show that it may be a special kind of immune cell called T-regulatory or Treg cells.
New Study Explains How Inflammation Causes Gastric Cancer [Kanazawa University] Using mouse models and human cancer cell lines, they showed that inflammation resulting from bacterial infection leads to the proliferation of gastric epithelial cells, which ultimately form gastric tumors. By blocking the protein pathway responsible for this proliferation, they prevented gastric tumor formation.
Unexpected findings reveal relationship between the amino acid leucine and tamoxifen resistance [Beth Israel Deaconess Medical Center] In follow up, Muthuswamy’s team is investigating whether a leucine restricted diet can prevent growth or enhance response to therapy for ER+ breast cancer cells in mice.
	5.12.10 IMMUNOTHÉRAPIES - FUSIONS ET ACQUISITIONS
Kiadis to buy CytoSen, adding June to advisory board [Fierce Biotech] Dutch biotech Kiadis has focused its efforts to date on T cell therapies, specifically a drug designed to improve outcomes in cancer patients who undergo partially matched, haploidentical hematopoietic stem cell transplants (HSCT). That drug, ATIR101, could come to market in Europe later this year and is on the road to the phase 3 data needed to win global approvals.
T cell experts at Kiadis bag CytoSen’s NK cell tech, plotting a dual cancer killing approach with tips from Carl June [EndPoints] Both companies have had the same goal: to boost the chances of cancer patients undergoing hematopoietic stem cell transplants by supercharging their immune system while their bone marrow recovers from the procedure.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Cellectis Announces Oral and Poster Presentations of Allogeneic CAR T-Cell Programs at the 2019 ASGCT Annual Meeting [Cellectis] An oral presentation will demonstrate the potential of UCARTCS1A as a treatment approach for patients with Multiple Myeloma. This presentation follows the recent clearance of the UCARTCS1A IND by the FDA, IRB approvals as well as clinical batch release.
In another CRISPR first, Penn researchers dose US cancer patients with gene-edited T cell therapy [EndPoints] The basic idea here is not unlike CAR-T, except with different elements and technologies: Take a patient’s T cells, engineer it to express NY-ESO-1 TCR, while eliminating TCR and PD-1 originally on the surface using CRISPR.
	5.2.3 PHARMA - ÉCONOMIE
Turning Point Prices IPO, Raising $166M to Test Cancer Drugs [Xconomy] Its lead candidate, repotrectinib, is a type of cancer drug called a kinase inhibitor, which is meant to target genes that are believed to play a role in causing tumors in patients with non-small cell lung cancer and advanced solid tumors.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
The king is dead, long live the king: Sharpless vows to continue Gottlieb era at FDA [Fierce Biotech] “So that’s what will steer my priorities as Acting Commissioner: a commitment to science-based decision-making and prioritizing our efforts for the benefit of the public health.”
Ned Sharpless is not playing with the FDA’s gold standard — any more than Scott Gottlieb did [EndPoints] In an all-hands-on-deck address to staffers, Sharpless promised to fit the Gottlieb mold perfectly, vowing to maintain the agency’s gold standard on drug approvals while doing what he can to keep the copycats coming to help tamp down on drug costs.
	5.4 TRAITEMENTS - ECONOMIE
Three cancer drugs cleared for NHS funding in Scotland [Cancer Research UK] The fresh batch of decisions from the Scottish Medicines Consortium last week included the approval of a targeted liver cancer drug, lenvatinib (Lenvima), for patients with a rare type of liver cancer, called hepatocellular carcinoma. The SMC also approved two drugs for some children and young adults with leukaemia. Both drugs – blinatumomab (Blincyto) and dasatinib (Sprycel) – are already approved to treat adults with the same disease profiles.
	5.5 ASCO
ASCO Announces Top Studies to Be Presented at 2019 Annual Meeting [ASCO] Advances in targeted therapies for pancreatic, prostate, and pediatric cancers, as well as new approaches to overcoming limited access to cancer care are among the topics that will be highlighted in the meeting’s official Press Program.
	5.5.1.1 ASCO (GÉNÉRAL) - INDUSTRIELS
Genmab Announces Data to be Presented at 2019 ASCO Annual Meeting [Genmab] A list of accepted industry sponsored abstracts is provided below, and includes ten daratumumab abstracts, two of which were accepted for oral presentations, one abstract on enapotamab vedotin, and two abstracts on tisotumab vedotin (Trial in Progress abstracts).
	6.1 OBSERVATION
Cervical Cancer Subtype Rising in Some Sub-Populations [ACS] Investigators examined trends in squamous cell carcinoma and adenocarcinoma incidence rates in the U.S. by age group, race/ethnicity, and stage at diagnosis using data from the U.S. Cancer Statistics Incidence Analytic Database.
	6.11 PATIENTS
The radiotherapy department can be hell, but it’s also a place you feel lucky [The Guardian] I’ve been accompanying my friend for six weeks of intensive cancer treatment – at first I dreaded it, but soon it came to feel like a privilege.