Onco Actu du 23 avril 2019

	2. ETIOLOGIE
Mice Inherit Cancer Susceptibility Via Epigenetic Changes in Sperm [The Scientist] Mouse fathers whose sperm lacks the gene Kdm6a pass down altered methylation patterns to male offspring, along with a better chance of developing tumors and dying.
	3.1 PRÉVENTION - TABAC
Parents using both e-cigarettes and traditional cigarettes may be more motivated to quit [Mass. General Hospital] Among a group of more than 700 parents who reported currently using cigarettes, 11 percent reported also using e-cigarettes, making them dual users of both products. Of 115 parents who reported using e-cigarettes, 70 percent were still smoking traditional cigarettes.
	3.3 PRÉVENTION - VACCINS
Could a Vaccine Prevent Colorectal Cancer in People with Lynch Syndrome? [NCI] People with Lynch syndrome would be candidates for a human cancer prevention vaccine, if one is developed. But less than 5% of the estimated 1.1 million people with Lynch syndrome know that they have it.
	3.6 PRÉVENTION - ACTIVITÉ PHYSIQUE
Why Does Exercise Guard Against Cancer? Inflammation May Play a Role [NY Times] A transitory increase in inflammatory markers after exercise might be helping to jam the proliferation of tumor cells, says Tina Skinner, a physiologist who was the senior author of the study.
	4. DÉPISTAGE, DIAGNOSTIC ET PRONOSTIC
The Doctors Believed That the Woman Had Leukemia. But Could That Explain Her Horrible Rash? [NY Times] When they tested the patient’s blood, the number of red blood cells and platelets was average, but her white-blood-cell count was extremely high — nearly 90,000, about nine times what is usually seen. And the cells themselves looked very abnormal. So, the doctor explained, it seemed likely that she had some kind of leukemia.
	4.10 DÉP., DIAG. & PRONO. - POUMON
A Deep-Learning Model May Help Predict Lung Cancer Survival and Outcomes [AACR] The investigators analyzed the model’s ability to make significant cancer outcome predictions with two datasets: the training dataset of 581 images and an independent validation dataset of 178 images from 89 patients with non-small cell lung cancer who had been treated with chemoradiation and surgery.
	4.12 BIOPSIES LIQUIDES
Blood samples to help select the right early phase clinical trials for cancer patients [Cancer Research UK] The authors caution that while this study is promising, not every patient will have identifiable and ‘druggable’ faulty genes in their blood, nor will every patient have the opportunity to receive a treatment tailored to their cancer.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
Molecular Profiling of Cancer Patients Uncovers Combination Treatments in I-PREDICT Study [Genome Web] Overall, the researchers reported a matching rate of 49 percent, based on all 149 individuals consented to the study. Other precision oncology trials of predetermined monotherapies often have much lower matching rates in the range of 5 percent to 10 percent, the researchers noted.
	5.10 TRAITEMENTS - ESSAIS
WINTHER Trial Highlights Challenges, Potential of Transcriptomics for Precision Oncology [Genome Web] This is the first trial to match patients with solid tumors to treatments based on transcriptomics, noted Vladimir Lazar, an investigator on WINTHER and chief scientific and operating officer of the WIN Consortium, the body organizing the study. While the trial may not have reached its prespecified endpoint, "the lessons in this trial and results are very important," Lazar said.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Redesigned CAR-T eliminates dangerous cytokine release syndrome in lymphoma trial [Fierce Biotech] When T cells were transduced with CD19-BBz(86) in the lab, they produced lower levels of cytokines but maintained their ability to kill CD19 tumor cells, the USC-led team reported. CD19-BBz(86) CAR-T cells did not cause CRS in mice.
With some tweaks, CAR-T cancer therapy could be made safer — and more widely available — study suggests [STAT] In the study, published in Nature Medicine, the remixed Kymriah led to no serious cases of cytokine release syndrome, an immunological flareup common in CAR-T, and no incidents of neurotoxicity.
	5.12.5 IMMUNOTHÉRAPIES - PHARMA
Poseida to Advance CAR-T For Myeloma with Novartis-Led $142M Round [Xconomy] Poseida is enrolling multiple myeloma patients who have failed multiple therapies into a Phase 2 trial in which patients will be followed on an outpatient basis, rather than in the hospital, following the treatment.
CAR-T maker Poseida forgoes IPO, hauls in $142M series C instead [Fierce Biotech] Currently, the autologous P-BCMA-101 is enrolling patients in a phase 2 study as an outpatient treatment, and the company plans to begin dosing before July. Poseida believes it can make headway in CAR-T safety, which remains a strong concern for the field.
Poseida Therapeutics Raises $142 Million in Series C Financing [Poseida] The company’s CAR-T product candidates are manufactured with Poseida’s non-viral piggyBac® DNA Modification System, resulting in a high percentage of stem cell memory T cells (TSCM). Tscm cells are the only T cell that is self-renewing and long-lived, potentially resulting in product candidates that are more efficacious, less toxic and more durable.
	5.12.6 IMMUNOTHÉRAPIES - AMM
Merck heaps early pressure on Bristol-Myers' Opdivo with Keytruda's kidney cancer debut [Fierce Pharma] The regimen will go up against an Opdivo-Yervoy pairing in one of the Bristol-Myers drug’s key indications, and analysts give Merck the advantage.
FDA Approves Merck’s KEYTRUDA® (pembrolizumab) in Combination With Inlyta® (axitinib) as First-Line Treatment for Patients With Advanced Renal Cell Carcinoma (RCC) [Merck] Approval Based on Results of KEYNOTE-426, Where KEYTRUDA in Combination With Axitinib Reduced the Risk of Death by Nearly Half Compared to Sunitinib.
As rivals wait in line, Merck’s Keytruda scores early FDA nod for frontline patients with the most common form of kidney cancer [EndPoints] Meanwhile, Pfizer and Germany’s Merck KGaA are not far behind. The FDA has agreed to a speedy review for their application to market a combination of their checkpoint inhibitor Bavencio and Inlyta in RCC patients — and the agency is expected to make its decision by June.
FDA approves pembrolizumab plus axitinib for advanced renal cell carcinoma [FDA] Approval was based on KEYNOTE‑426 (NCT02853331), a randomized, multicenter, open-label trial conducted in 861 patients who had not received systemic therapy for advanced RCC.
Merck's Keytruda wins FDA approval as combination therapy for kidney cancer [Reuters] The drug was approved in combination with Pfizer Inc’s Inlyta to treat advanced renal cell carcinoma.
	5.2.3 PHARMA - ÉCONOMIE
Big Pharma Cuts, Current and Coming [In The Pipeline] Word came out just before the weekend (first at Endpoints) that GlaxoSmithKline is laying off R&D employees at both Stevenage (UK) and Upper Providence (US). Current leadership is re-organizing drug discovery efforts to put more emphasis on oncology, immunology and genetic-linked disease, and this moves seems linked to that.
How biopharma companies use NIH and vice versa [EndPoints] From 1988 to 2004, NIH entered into almost 2,500 license agreements and generated more than $500 million in royalty revenues. More recently, royalties have amounted to more than $100 million per year.
	5.9 AACR
AACR Annual Meeting 2019: Patients as Partners in the Research Process [Cancer Research Catalyst] “We are witnessing a culture shift in how patients participate in cancer research,” Jaffee said. “This process is driven by patients, survivors, and their families, and it’s becoming an integral part of cancer research.”
	6.12 ETHIQUE
Safeguards for human studies can’t cope with big data [Nature] Continued acceptance of the lack of guidelines is an abrogation of the research community’s ethical duties. We should call on Congress, in parallel with international bodies such as the World Health Organization, to authorize a national commission to write another Belmont Report to deal holistically with applications of data science that will only become more complicated as technology progresses.
	6.6 PUBLICATIONS
Harvard cancer lab subject to federal misconduct probe [Retraction Watch] Sam W. Lee, a Harvard researcher — or perhaps former Harvard researcher — who has lost three papers to retraction, including one from Nature, now has an expression of concern for another article, this one in Molecular and Cellular Biology.
	6.7.1 IA/BIOINFORMATIQUE
New Bioinformatics Portal Provides One-Stop Shop for Multi-Omics Data Analysis [Genome Web] Metascape is designed to provide a comprehensive gene list annotation and analysis resource for experimental biologists. It combines functional enrichment, interactome analysis, gene annotation, and membership search from over 40 independent knowledgebases spanning 10 common model organisms.
Crowdsourced AI learns to target lung tumors for radiation [Reuters] To determine whether artificial intelligence could fill the void, Mak and his colleagues set up a contest on a website called Topcoder.com that hosts challenges for a community of more than a million programmers around the world, who compete for prizes by solving computational problems.
	6.8 COMMUNICATION
Case Reports in the Age of Twitter [The American Journal of Medicine] “Do you believe he is posting those films? Isn't that identifiable? Did she get consent?” These are concerns we fear our patients have and believe are already affecting our physician patient relationships.
	6.9 CONTROVERSES
Wary of Chinese Espionage, Houston Cancer Center Chose to Fire 3 Scientists [NY Times] The center said it did not have information about any of the scientists’ nationalities. But in redacted investigative reports, the center referred to ties to China or Chinese residents or institutions in all three cases.
Three Researchers Ousted from MD Anderson [The Scientist] The center had received letters from NIH about researchers’ violations of granting agency policies and intellectual property theft in 2018.
MD Anderson addresses national threat of foreign influence [MD Anderson Cancer Center] As the recipient of taxpayer and donor support for innovative research, MD Anderson is focused on protecting the institution, its people and its resources. Steps have been taken to safeguard the institution, including development of a cutting-edge approach to Enterprise Risk Management.
Exclusive: Major U.S. cancer center ousts ‘Asian’ researchers after NIH flags their foreign ties [Science] Chinese American community fears ethnic targeting at MD Anderson by the Federal Bureau of Investigation and National Institutes of Health.