Onco Actu du 11 septembre 2019

	1. BIOLOGIE
Breast Cancer Cells 'Stick Together' to Spread Through The Body During Metastasis [Johns Hopkins] Study reveals that E-cadherin, a molecule that allows cells to stick to each other, promotes metastasis in the most common type of breast cancer.
The structure of a T-cell mechanosensor [Nature] T-cell receptors orchestrate immune-system responses against infection and cancer. A structure of an entire T-cell receptor complex clarifies its assembly and signalling, and sheds light on its dynamic ligand recognition.
	1.5 PRIX LASKER
Celebrating the 2019 Lasker Awards: A Cell Collection [Cell] In this year’s collection, which includes opening remarks from Joseph L. Goldstein, Chair of the Albert Lasker Medical Research Awards jury, we present features on the scientific achievements underpinning the awards, and we hear from the winners themselves as they recount their unique paths to scientific and medical progress.
Lasker Awards Honor Advances in Modern Immunology [NY Times] The prizes recognized the discoverers of B and T lymphocytes, pioneers in genetic engineering to fight breast cancer, and a nonprofit that helps get vaccines to the world’s poorest children.
The Team that Just Wouldn’t Quit and a New Paradigm in Cancer Drug Discovery [Cell] Receiving the Lasker award for Clinical Medical Research is a staggering event. Perhaps equally staggering is the fact that as many as 2 million women worldwide have now been treated with Herceptin (trastuzumab), many of whom benefited from the treatment. This accomplishment is wonderfully rewarding for everyone who has been involved.
Immune-cell pioneers win prestigious Lasker medical award [Nature] Two scientists who discovered the roles of key immune cells have won one of the 2019 Lasker medical-research awards — prizes often dubbed the American Nobels.
Discovery of 2 Distinctive Lineages of Lymphocytes, T Cells and B Cells, as the Basis of the Adaptive Immune System and Immunologic Function [JAMA] The 2019 Albert Lasker Basic Medical Research Award has been presented to Max Dale Cooper and Jacques F. A. P. Miller for discovery of the 2 distinct classes of lymphocytes, B and T cells, a monumental achievement that provided the organizing principle of the adaptive immune system and launched the course of modern immunology.
Biomarker-Driven Drug Discovery in Cancer—Trastuzumab Development [JAMA] The 2019 Lasker-DeBakey Clinical Medical Research Award has been presented to H. Michael Shepard, Dennis J. Slamon, and Axel Ullrich for the invention of trastuzumab, the first monoclonal antibody that blocks a cancer-causing protein, and for its development as a life-saving therapy for women with breast cancer.
Moving from Cancer Genetics to Therapy [Cell] Cell editor Lara Szewczak spoke with Dennis, the recipient of the 2019 Lasker-DeBakey Clinical Medical Research Award, to discuss the research leading to trastuzumab and his views on how current progress in treating cancers may impact the US health care system.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
Is Juul the new big tobacco? Wave of lawsuits signal familiar problems [The Guardian] Vapes were once seen as safe alternatives to smoking, but now the biggest US vape-maker faces similar issues to cigarette companies.
Bloomberg Takes on Vaping After Giving $1 Billion to Fight Tobacco [NY Times] New York’s former mayor has committed $160 million to ban flavored e-cigarettes amid a series of efforts designed to increase oversight of the industry.
Factbox: What we know about U.S. vaping illnesses [Reuters] U.S. public health officials are investigating more than 450 cases of severe lung illnesses and have confirmed at least five deaths related to electronic cigarette products including the devices and liquids used inside them.
	4. DÉPISTAGE, DIAGNOSTIC ET PRONOSTIC
European Labs Continue to Validate and Implement TMB, Facing Down Cutoff Discordance Concerns [Genome Web] In the study, Jermann and colleagues measured TMB retrospectively using the Thermo Fisher Oncomine assay in 76 metastatic non-small cell lung cancer patients and used data on response and outcomes to define a cutoff to subcategorize the group into low, intermediate, and high TMB.
	4.12 BIOPSIES LIQUIDES
New blood test for prostate cancer is highly-accurate and avoids invasive biopsies [Queen Mary University of London] The new prostate cancer test (the Parsortix® system from ANGLE plc) detects early cancer cells, or circulating tumor cells (CTCs), that have left the original tumour and entered the bloodstream prior to spreading around the body.
Simple blood test for prostate cancer could save men from needless biopsies and 'over-treatment' [The Telegraph] The study, published in the Journal of Urology, looked at the use of the CTC test in 98 pre-biopsy patients and 155 newly diagnosed prostate cancer patients enrolled at St Bartholomew's Hospital in London.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
When should NHS contact patients over faulty genes? [University of Exeter] The NHS and health services worldwide need to develop policies on when patients should be “re-contacted” about faulty genes, as the current lack of guidance creates a dilemma for health services, experts have warned.
Scientists call for population wide BRCA testing for higher risk group [Queen Mary University of London] Following a Queen Mary University of London study, researchers are calling for population wide BRCA testing in the Jewish community after finding it to be more effective than current approaches, cost effective and had a high satisfaction rate with those undergoing testing.
	5.12.13 IMMUNOTHÉRAPIES - BIOMARQUEURS
A Liquid Biopsy Test Can Identify Patients Who May Respond to Immune Checkpoint Blockade [AACR] They developed a 98 kb pan-cancer 58-gene panel, then employed a multifactorial error-correction method and a novel peak-finding algorithm to identify MSI frameshift alleles in cell-free DNA (cfDNA). The study was based on 61 patients with advanced cancer and 163 plasma samples from healthy individuals.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Italian gene therapy player draws new investor from China for its answer to CAR-T relapses [EndPoints] The idea of the Genenta therapy, called Temferon, is to prevent those relapses by rebuilding the patient’s immune system within the tumor sites themselves, called TEMS. The treatment involves injecting a lentivirus for a gene transfer in hematopoietic stem and progenitor cells, triggering interferon-αexpression in the targeted areas. The patient would then be able to fight off future relapses.
	5.13 WCLC
At Big Lung Cancer Meeting, Lights Shine on KRAS, Drug Combos & More [Xconomy] Xconomy rounded up some of the most noteworthy headlines and put them in context below.
	5.13.1 WCLC - IMMUNOTHÉRAPIES
WCLC: Roche's Tecentriq comes up short in squamous lung cancer, leaving Merck's Keytruda 'unchallenged' [Fierce Pharma] The Swiss drugmaker Tuesday unveiled results showing that its Tecentriq-chemo combo failed to outdo solo chemo at extending the lives of previously untreated patients. Those receiving the Tecentriq pairing lived a median 14.2 months, which wasn’t enough to significantly top the 13.5 months chemo posted.
WCLC: Bristol-Myers' Opdivo spurs fivefold increase in long-term lung cancer survival [Fierce Pharma] In other words, “one out of three patients who responds” to Opdivo is “still responding at five years,” Sabine Maier, M.D., the company’s development lead for thoracic cancers, noted.
IMpower131: Final Overall Survival Results of Carboplatin + Nab-Paclitaxel ± Atezolizumab in Advanced Squamous NSCLC [IASLC] The multi-center trial enrolled 1021 patients— the 343 patients in Arm B received atezolizumab + carboplatin + nab-paclitaxel 100 mg/m2 qw. There were 340 patients enrolled in Arm C who received carboplatin + nab-paclitaxel for four or six cycles followed by best supportive care.
KEYNOTE-024 Three-Year Survival Update: Pembrolizumab Effective as First-Line Therapy for Advanced Non–Small-Cell Lung Cancer [IASLC] The median overall survival length among patients in the pembrolizumab arm was 26.3 months compared to 14.2 months in the chemotherapy arm.
Pooled Analysis Continues to Show Merck’s KEYTRUDA® (pembrolizumab) in Combination with Chemotherapy Improved Overall Survival Versus Chemotherapy Alone as First-Line Treatment for Patients with Advanced NSCLC Whose Tumors Do Not Express PD-L1 [Merck] Results – from KEYNOTE-189, KEYNOTE-407 and KEYNOTE-021 (Cohort G) – were consistent with those observed in the overall study populations across all three trials.
Patients Taking Nivolumab Experience Five-Fold Increase in Overall Survival Compared to Chemotherapy [IASLC] In CheckMate 017 and 057, 854 patients with advanced NSCLC, ECOG performance status 0 to 1, and progression during or after first-line platinum-based chemotherapy, were randomized 1:1 to nivolumab or docetaxel until progression or unacceptable toxicity.
Bristol-Myers Squibb Announces Pooled Five-Year Survival Results for Opdivo (nivolumab) in Previously-Treated Advanced Non-Small Cell Lung Cancer Patients [BMS] Longest survival follow-up from a pooled analysis of randomized Phase 3 trials of an Immuno-Oncology therapy in this setting demonstrated a greater than five-fold increase in five-year overall survival rates; 13.4% for Opdivo and 2.6% for docetaxel.
	5.13.1.1 WCLC - BIOMARQUEURS
WCLC: Merck's Keytruda dispels 'urban legend' with latest lung cancer survival win [Fierce Pharma] “There is this notion out there that somehow chemo combo is less effective with PD-L1 negatives, and frankly the data just don’t support that at all,” Roy Baynes, M.D., Merck SVP and head of global clinical development, said.
Biomarker data help Merck case for wide use of Keytruda combo [Biopharma Dive] While data from KEYNOTE-189 already supported broad use of Keytruda together with chemo, Merck's pooled analysis helps reinforce that conclusion further.
	5.13.4 WCLC - DIVERS
Europeans Face Significant Challenges to Participate in Lung Cancer Clinical Trials [IASLC] The survey was shared with patients with lung cancer across Europe and those who took part resided mostly in Poland (19.5 percent), Italy (18.7 percent), Denmark (9.9percent) and Spain (9.2 percent).
	5.3 TRAITEMENTS - FDA, EMA, NICE...
Frontrunner to lead FDA, dogged by controversies, has developed knack for confronting them [STAT] Hahn, a 59-year-old oncologist, is an accomplished researcher and longtime GOP donor. He has risen through the ranks at MD Anderson since beginning there in 2015, first as the division head for radiation oncology, then as chief operating officer, then as chief medical executive.
	5.6 ESMO
GSK to present data from its innovative oncology portfolio at ESMO Congress 2019 [GSK] Full results from the pivotal PRIMA study of Zejula (niraparib) in ovarian cancer to be presented in a Presidential Symposium.
	6.6 PUBLICATIONS
Open-access megajournals lose momentum as the publishing model matures [Science] Concerns include declining volume, slower publication, and softening citation measures.
What’s next for Registered Reports? [Nature] Reviewing and accepting study plans before results are known can counter perverse incentives. Chris Chambers sets out three ways to improve the approach.
Rise of the platforms [Nature Physics] Facebook and Google connect advertisers, businesses and everyday users. Uber connects riders and drivers. And the online platforms of major journals connect scientists that may variously act as authors, readers and reviewers.
	6.7 DMP, BIG DATA & APPLIS
Google, Mayo Clinic strike sweeping partnership on patient data [STAT] The 10-year partnership is a testament to Google’s expanding role in the U.S. health care system and gives Mayo greater access to the engineering talent and computing resources it needs to embed its expertise in algorithms and commercial devices.