Onco Actu du 22 juillet 2019

	1. BIOLOGIE
Cancer trades in sugar for fatty acids in order to spread around the body [Institute of Cancer Research] The research raises the opportunity to screen breast cancer patients for increased levels of AKR1B10, which may help identify patients at an increased risk of metastatic relapse.
Study hints at why an aggressive form of brain cancer is hard to treat [Broad Institute] The researchers profiled gene expression in more than 24,000 tumor cells from 20 adult and eight pediatric glioblastoma patients and also analyzed glioblastoma models in the lab.
Crunching the Numbers of Cancer Metastasis [Beth Israel Deaconess Medical Center] While revealing that metastatic breast cancer cells alter their shape to spread to other regions of the body, researchers develop a mathematical model that can be applied to study similar cellular systems.
New research unfolds the DNA “origami” behind brain cancers [OICR] A collaborative study, recently published in Genome Research, has mapped the three-dimensional configuration of the genome in glioblastoma and discovered a new way to target glioblastoma stem cells – the self-renewing cells that are thought to be the root cause of tumour recurrence.
How DNA outside cells can be targeted to prevent the spread of cancer [Tokyo University of Science] Cell-free DNA in blood is used for prenatal screening and tumor diagnosis/prognosis. Scientists now provide evidence for its generation and show that it can be used to prevent the spread of tumors.
	2. ETIOLOGIE
Low doses of radiation promote cancer-capable cells [Sanger Institute] New research in mice helps to understand the risks around exposure to low doses of radiation, such as CT scans and x-rays.
	2.11 ETIOLOGIE - ALIMENTATION
Daily coffe doesn't affect cancer risk [QIMR Berghofer] Senior author and head of QIMR Berghofer’s Statistical Genetics Group, Associate Professor Stuart MacGregor, said the large Mendelian randomization study looked at data from more than 300,000 people and showed drinking coffee every day neither reduced nor increased a person’s risk of developing any cancer.
Coffee doesn't increase cancer risk, researchers find [ABC} Drinking coffee does not change a person's risk of being diagnosed with or dying from cancer, a new Queensland study has found, with researchers saying the results could have public health implications worldwide.
	2.5 ETIOLOGIE - GÈNES
Discovery of Novel Susceptibility Loci and Genes for Prostate Cancer Risk [ESMO] Results from a transcriptome-wide association study in over 140,000 European descendants.
	2.6 ETIOLOGIE - ENVIRONNEMENT
U.S. judge slashes Roundup jury award to $25.3 million; Bayer still plans to appeal [Reuters] “Monsanto’s conduct, while reprehensible, does not warrant a ratio of that magnitude, particularly in the absence of evidence showing intentional concealment of a known or obvious safety risk,” Chhabria wrote.
	3.1 PRÉVENTION - TABAC
NHS could save billions by offering cash reward to quit smoking [The Guardian] Quitters 50% more likely to succeed if offered a financial incentive, researchers find.
To Help Smokers Quit, Pay Them [NY Times] The meta-analysis, in the Cochrane Reviews, covered 33 trials and included more than 21,000 people. The studies were carried out in various settings — primary care clinics, universities, cancer treatment centers and others. All followed the participants for at least six months, checking breath or body fluids for evidence of smoking.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
Flavored e-cigs appeal to new nicotine users, Stanford study finds [Stanford Medicine] "Collectively, the evidence points to needed regulation of all flavored tobacco products, including mint and menthol," they write. "By eliminating the sale of all flavored tobacco, these products will be less appealing to youth and young adults."
Vaping may aid smoking cessation but also boost relapse risk [Reuters] Adults who smoke cigarettes may have an easier time cutting back or quitting altogether if they start vaping, but a new French study also suggests that vaping may make ex-smokers more likely to relapse.
	4. DÉPISTAGE, DIAGNOSTIC ET PRONOSTIC
Improving Cancer Diagnosis and Care Clinical Application of Computational Methods in Precision Oncology: Proceedings of a Workshop [National Academies Press] The second workshop, conducted in collaboration with the Board on Mathematical Sciences and Analytics, was held in October 2018 to examine the use of multidimensional data derived from patients with cancer, and the computational methods that analyze these data to inform cancer treatment decisions. This publication summarizes the presentations and discussions from the second workshop.
	4.10 DÉP., DIAG. & PRONO. - POUMON
Investigators identify potential markers of lung cancer in paired blood and tissue samples [Mass. General Hospital] Study may help develop a simple blood test to identify patients who warrant low-dose CT screening for lung cancer.
	4.12 BIOPSIES LIQUIDES
Inivata to Test Liquid Biopsy Against Tissue Sequencing in French Prospective Clinical Trial [Genome Web] The randomized Phase III interventional trial is called LIquid Biopsy for the Early detection of LUng cancer LEsion (LIBELULE). Investigators plan to enroll at least 286 patients across 17 clinical sites in France.
	4.13 DÉP., DIAG. & PRONO. - PEAU
Evidence for the benefits and harms of screening for malignant melanoma [Cochrane] This review shows that adult general population screening for malignant melanoma is not supported or refuted by current evidence from randomised controlled trials and therefore does not fulfil well-established screening criteria.
	4.16 DÉP., DIAG. & PRONO. - PANCRÉAS
An experimental AI system can predict when pancreatic cysts will become cancerous [STAT] A study published in Science Translational Medicine detailing the performance of the system, dubbed CompCyst, reported that its use would have reduced 60% of unnecessary surgeries in patients whose tumors were found not to be harmful following their procedures.
	4.9 DÉP., DIAG. & PRONO. - SEIN
Curtis: Women are intrigued by the many questions asked in TMIST [The Cancer Letter] We are gathering more granular demographic and socioeconomic data about women eligible to participate in TMIST—both those who enroll and those who choose not to enroll. I’m excited that in addition to helping tailor breast cancer screening, we will also know who participates in clinical trials and what barriers prevent others from doing so.
	5. TRAITEMENTS
UK cancer treatment ‘revolution’ as survey finds third of patients receiving modern precision treatments [Institute of Cancer Research] The Institute of Cancer Research, London, conducted the survey of more than 1,000 cancer patients to provide a ‘state of the nation’ overview of cancer treatment, ahead of completion of its new £75 million Centre for Cancer Drug Discovery.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
A heart drug could significantly increase survival rates for children with an aggressive form of brain tumour, says new study [University of Nottingham] The findings, published in Scientific Reports and led by experts in the University’s Schools of Medicine and Life Sciences, suggest that co-treatment with a drug normally used to treat cardiac hypertrophy can overcome chemotherapy resistance and increase survival in over a third of ependymoma patients.
Cancer Device Created at Rutgers to See if Targeted Chemotherapy is Working [Rutgers] “Our technology combines artificial intelligence and sophisticated biosensors that handle tiny amounts of fluids to see if cancer cells are sensitive or resistant to chemotherapy drugs.”
Making cancer stem cells visible to the immune system - New results may enable innovative treatment concept against leukemia [DKFZ] The results provide the basis for the possibility of combating malignant leukemia stem cells by combining PARP inhibitors with active NK cells. The scientists involved are now planning to evaluate this approach in a clinical study.
	5.10 TRAITEMENTS - ESSAIS
GSK poses challenge to rival AstraZeneca with positive PARP data [Biopharma Dive] Topline results from the Phase 3 PRIMA study show GSK's Zejula, which inhibits a DNA repair enzyme called PARP, significantly improved progression free survival over placebo when used as a first-line maintenance treatment following platinum-based chemotherapy.
GSK's Zejula racks up first-line maintenance win in ovarian cancer, even in non-BRCA patients [Fierce Pharma] Zejula will have to stand up to AstraZeneca and Merck's rival med Lynparza, which has a lead in that market, thanks to a December approval for first-line, BRCA-mutated patients after platinum chemo. But the GSK drug's data win covers patients without BRCA mutations, too, giving it a chance to win a chunk of the market Lynparza doesn't yet own.
A bird’s-eye view of clinical trials provides new perspectives on drug research and development [STAT] I believe this bird’s-eye perspective, presented with an interactive visualization, can empower all of us to better understand trials by revealing the geography, the forests, and the trees of clinical testing, and helping us start to imagine new possibilities for how we might shape the landscape to better serve all of our interests.
N-of-1 Trials Take on Challenges in Health Care [The Scientist] From personalizing clinical practice to aiding biomedical research, individualized clinical trials have been heralded as a solution to several problems plaguing modern medicine. But they’ve yet to be widely adopted.
GSK announces positive headline results in Phase 3 PRIMA study of ZEJULA (niraparib) for patients with ovarian cancer in the first line maintenance setting [GSK] Niraparib demonstrates significant improvement in progression free survival for women regardless of their biomarker status.
GSK drug helps ovarian cancer patients live longer in late-stage study [Reuters] For GSK, the success of Zejula would help it access a wider population group and give it an edge over rival PARP inhibitors such as AstraZeneca and Merck & Co’s Lynparza and Clovis Oncology’s Rubraca.
	5.12 IMMUNOTHÉRAPIES
Pioneering immunotherapy drug gets new testing for early prostate cancer [Stanford Medicine] Provenge is now enjoying a revival, thanks to a large new clinical trial that will test it in men with early cancer, a point in which some clinicians believe it will be most useful.
	5.12.1 IMMUNOTHÉRAPIES - PARTENARIATS
Bayer, Bristol-Myers Squibb and Ono Pharmaceutical Enter Into a Clinical Collaboration Agreement to Investigate Stivarga® (regorafenib) and Opdivo® (nivolumab) as Combination Therapy in Patients With Metastatic Colorectal Cancer [BMS] Combination of regorafenib and nivolumab vs. regorafenib alone to be evaluated in patients with micro-satellite stable metastatic colorectal cancer.
	5.12.10 IMMUNOTHÉRAPIES - FUSIONS ET ACQUISITIONS
Boehringer Ingelheim Acquires AMAL Therapeutics, Significantly Enriching Its Cancer Immunology Portfolio with Novel Cancer Vaccines Platform [Boehringer Ingelheim] Acquisition adds key platform supporting Boehringer Ingelheim’s focus on patients with difficult-to-treat gastrointestinal and lung cancers.
	5.12.11 IMMUNOTHÉRAPIES - PRÉ-CLINIQUE
Improving Cancer Immunotherapy: Overcoming the Problem of ‘Exhausted’ T Cells [NCI] Research groups from around the globe have now identified several proteins that appear to play a central role in transforming T cells from powerful destroyers to depleted bystanders with limited capacity to harm cancer cells.
Unmasking mutant cancer cells [MIT] “Hopefully, our findings can reinvigorate interest in HSP90 inhibition as a complementary approach for immunotherapy.”
Cancer cells reconnect with their inner child to evade immunotherapy [Fred Hutch] A team of scientists found that a gene called DUX4 — usually turned on just after an egg is fertilized — allows tumor cells to become invisible to attacking immune cells. DUX4 may help to explain why checkpoint inhibitors, a type of immunotherapy that unleashes a patient’s own immune system against their cancer, do not work in all patients.
Discovery shows how difficult-to-treat prostate cancer evades immune system [MD Anderson Cancer Center] Study reports pre-clinical development of novel treatment and potential for combination use with immunotherapy drugs.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Precision BioSciences backs off-the-shelf cancer cell therapy effort with new manufacturing plant [EndPoints] “[The plant] also has the potential to be a commercial launch facility with the capacity to generate up to 10,000 doses of CAR T cell therapies and 4,000 doses of gene therapies per year,” he added.
Takeda's translational cell therapy group revs up for a race to the clinic with off-the-shelf CAR-T [EndPoints] Wildt and his crew are ramping up a dozen autologous cancer programs, each of which has the potential to pivot into an off-the-shelf allogeneic effort.
Keen to stay out front in cell therapy, Gilead's Kite builds its own viral vector manufacturing operations [EndPoints] Right now, Kite gets it viral vectors — critical starting material for editing the T cells to activate cancer-killing capabilities — from contract manufacturers, said Tim Moore, EVP of technical operations. But amid a cell therapy boom, the limits that place on commercial supply and development is becoming more apparent.
The Promises and Price of Cellular Therapies [New Yorker] New “living drugs”—made from a patient’s own cells—can cure once incurable cancers. But can we afford them?
Supercharging CAR-T with cancer vaccine, MIT team spotlights some new tech underpinning Darrell Irvine's startup [EndPoints] By sending a vaccine directly to the lymph nodes to stimulate CAR-T cells, he explains, they hit two birds with one stone: Preventing vaccines from getting degraded and CAR-T cells from releasing toxic cytokines — both of which happen in bloodstreams. And it combines the promises of both therapies.
T Cell Proliferation Linked to CAR T Responses [The Scientist] The results “confirm that T cells collected from patients with CLL tend to be of poor quality,” and provide valuable clues about why the therapy works only in certain patients, says Michel Sadelain, an immunologist at Memorial Sloan Kettering Cancer Center who didn’t work on the study.
	5.12.3 IMMUNOTHÉRAPIES-COMBINAISONS
Advancing Progress in the Development of Combination Cancer Therapies with Immune Checkpoint Inhibitors [National Academies Press] This workshop convened stakeholders with a broad range of expertise, including cancer researchers, clinicians, patient advocates, and representatives from industry, academia, and government. This publication summarizes the presentations and discussions from the workshop.
	5.12.5 IMMUNOTHÉRAPIES - PHARMA
Bayer, Longwood back star researcher's deep dive into the tumor microenvironment for new I/O targets [EndPoints] Steinberg, the CEO, is tight-lipped about the exact nature of their work except that they are brand new targets that, to the best of their knowledge, are not in any disclosed clinical pipelines anywhere.
	5.12.7 IMMUNOTHÉRAPIES - VACCINS
Neon’s Early Vaccine Study Is a Peek at Immunotherapy’s Third Wave [Xconomy] The results “look promising” but come with plenty of caveats, according to the study’s lead investigator. “I wouldn’t say I’m convinced that this has activity. We don’t know,” said Patrick Ott, the clinical director of Dana Farber Cancer Institute’s Center for Immuno-Oncology in Boston.
Neon to advance cancer vaccine after early results suggest added benefit [Biopharma Dive] Neon's most advanced candidate, dubbed NEO-PV-01, is custom made for each individual patient, designed to target tumor-specific proteins known as neoantigens.
In a small study, a cancer vaccine assist beats immunotherapy drugs alone [STAT] The Phase 1b study is the first to show improved outcomes in cancer patients receiving a neoantigen vaccine, which boosts production of immune cells that specifically target rogue molecules on the surface of tumor cells. But the trial comes with several caveats.
Personalized Cancer Vaccines in Clinical Trials [The Scientist] The field is young, but predicting antigens produced by patients’ malignant cells could yield successful treatments for individuals with a range of cancer types.
	5.2.1 PHARMA - PARTENARIATS
Broad Institute launches academic-industrial consortium for cancer dependency studies [Broad Institute] The Cancer Program of the Broad Institute of MIT and Harvard has established a new academic-industrial partnership program, the Cancer Dependency Map (DepMap) Consortium. This new endeavor will support efforts to discover promising treatment targets in cancer as well as biomarkers for identifying patient populations most likely to benefit from ongoing treatment discovery efforts.
	5.2.2 PHARMA - FUSIONS & ACQUISITIONS
AbbVie bets on early immuno-oncology asset [Biopharma Dive] STING activates immune cells that can attack tumors. Experimental STING activators are viewed as potential complements to Keytruda (pembrolizumab) and Opdivo (nivolumab), which turn off cancer's mechanisms for escaping immune response.
AbbVie Enhances Early Stage Oncology Pipeline with Acquisition of Mavupharma [AbbVie] Mavupharma's lead clinical candidate is MAVU-104, a first-in-class, orally active, small molecule inhibitor of ENPP1, an enzyme involved in the regulation of the STING pathway. Inhibiting ENPP1 activity with MAVU-104 allows for highly controlled enhancement of STING signaling in tumors without the need for injections.
AbbVie beefs up the oncology pipeline, bagging an upstart STING player with its own unique approach [EndPoints] Stimulating STING has been a big disappointment in biopharma, with setbacks at Merck and Aduro. But Mavupharma was focused on its own target: ENPP1, which they say acted as a “negative regulator” of STING.
	5.2.3 PHARMA - ÉCONOMIE
Roche doomsday is here: Long-feared Herceptin, Avastin biosims bust into U.S. market [Fierce Pharma] Both drugs will launch at a wholesale list price 15% cheaper than their reference biologics, the companies said.
Chasing Roche's aging blockbuster franchise, Amgen/Allergan roll out Avastin, Herceptin knockoffs at discount [EndPoints] While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.
Denmark's Genmab hits the jackpot with $500M+ US IPO as smaller biotechs rake in a combined $147M [EndPoints] There are at least five such products — which Genmab has fondly christened “knock-your-socks-off antibodies” — including an antibody-drug conjugate (ADC) called tisotumab vedotin being co-developed with Seattle Genetics, and another ADC called enapotamab vedotin that the company fully owns.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
Patient registries may prove valuable in regulatory decisions, EMA study finds [EndPoints] The authors explain how such registries can be used when randomized controlled trials are not feasible, such as with some rare diseases, or to meet postmarketing commitments.
PRAC recommends new measures to avoid dosing errors with methotrexate [EMA] The PRAC recommendations will now be sent to the Committee for Medicinal Products for Human Use (CHMP), which will adopt an opinion. Healthcare professionals will be informed in writing of the above changes. Patients who have any concerns about their medicine in the meantime should discuss them with their doctor or pharmacist.
	5.4 TRAITEMENTS - ECONOMIE
Novartis’ Kisqali, trailing Lilly’s Verzenio, nabs limited NICE backing in breast cancer [Fierce Pharma] Rather than a full nod, Kisqali’s reimbursement on NHS is available only through the Cancer Drugs Fund, which requires a patient’s application. That's the same limitation NICE gave Verzenio in its own recommendation this April.
Breast cancer patients to have further NICE-approved drug combination option on Cancer Drugs Fund [NICE] The draft guidance recommends ribociclib (also called Kisqali and made by Novartis) used with fulvestrant as an option for people with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer who have had previous endocrine therapy.
Second breast cancer treatment combo added to England's Cancer Drugs Fund [Cancer Research UK] The treatment combo of ribociclib (Kisqali) and fulvestrant (Faslodex), which was shown to slow disease progression in a clinical trial, was initially rejected for use by NICE in April 2019 over concerns the drugs didn’t provide value for money.
	5.9.5 AACR - CAR-T, THÉRAPIES CELLULAIRES
Immune Cell Therapy Shows Early Promise for Patients With Pancreatic Cancer [AACR] A nonengineered, multiantigen-specific T-cell therapy was safe, tolerable, and showed signs of clinical activity in patients who had pancreatic adenocarcinoma, according to preliminary results from a phase I clinical trial presented at the AACR special conference on Immune Cell Therapies for Cancer, held July 19–22.
What’s New in Immune Cell Therapy Research? [Cancer Research Catalyst] To inspire new breakthroughs in the cutting-edge field of immune cell therapy research, the AACR is holding a special conference, Immune Cell Therapies for Cancer: Successes and Challenges of CAR T Cells and Other Forms of Adoptive Therapy, this week in San Francisco.
	6. LUTTE CONTRE LES CANCERS
Why Dogs Now Play a Big Role in Human Cancer Research [Wired] There’s a strong chance your aging dog will get cancer—but your pupper could also help humans survive it.
Why cancer innovation must go beyond medicine: The C3 Prize search for ideas with the greatest potential for impact [The Cancer Letter] While the C3 Prize has proven to be an incredibly successful endeavor, it has also taught me a few important lessons about how we can better identify and support innovative ideas.
	6.1 OBSERVATION
Skin cancer rates rocket by 45% in 10 years [Cancer Research UK] Rates have increased by more than a third (35%) for women and by almost three-fifths (55%) for men.
Skin cancer rates have soared by 45 per cent in a decade as legacy of package holidays hits [The Telegraph] Overall, the jump was from 18 cases per 100,000 people to 26. Melanoma is the fifth most common cancer in the UK, with around 16,000 diagnoses is annually and 2,285 deaths.
Early risers may have lower breast cancer risk [Reuters] For the current analysis, researchers analyzed genetic variants associated with three sleep traits: sleep duration, insomnia, and a so-called morning or evening chronotype, referring to early or late risers. They looked at data on 180,216 women in the UK Biobank study and 228,951 women in the Breast Cancer Association Consortium (BCAC) study.
	6.10.1 POLITIQUES (USA)
Canada warns U.S. against drug import plans, citing shortage concerns [Reuters] Canada opposes any U.S. plans to buy Canadian prescription drugs that might threaten the country’s drug supply or raise costs for its own citizens, officials have told U.S. authorities, in a new setback to the Trump administration’s efforts to tackle high drug prices, according to documents obtained by Reuters.
Who’s the toughest on drug prices? A game of political one-upmanship is driving the policy debate in Washington [EndPoints] Whatever happens, biopharma will find itself pilloried at every campaign stop as the candidates pitch in with a popular and entirely bipartisan populist theme, shriveling the industry’s rep at a time drug hunters are enjoying unprecedented success in gaining substantial financial backing for research.
There Is No Single, Best Policy for Drug Prices [NY Times] Most Americans would like the government to act, but a one-size-fits-all approach is unlikely to be the answer.
Biden cancer group shuts down operations [Reuters] “We are suspending activities given our unique circumstances We remain personally committed to the cause, but at this time will have to pause efforts,” Greg Simon, president of the Biden Cancer Initiative, said in a statement. The group said on its website that it had shuttered as of July 11.
	6.3 ASSOCIATIONS/FONDATIONS
Cancer Research UK funding tops half a billion pounds [Cancer Research UK] Cancer Research UK raised £540m in fundraising income in the last financial year, an increase of 2 per cent over the previous year, in one of its most successful fundraising years so far.
Many of the deadliest cancers receive the least amount of research funding [Northwestern University] The nationwide study, conducted between October 2017 and February 2018, used IRS tax records to identify all nonprofit organizations that support any type of cancer and made at least $5 million in annual revenue in 2015. The scientists examined 119 organizations with a total of $5.98 billion in annual revenue.
	6.5 MÉDECINES ALTERNATIVES/COMPLÉMENTAIRES
How to survive the fake news about cancer [The Guardian] That pseudoscience is being hawked to vulnerable patients isn’t a new problem – cancer scams have existed for decades, and combating them was the impetus behind the 1939 Cancer Act. The substantial difference now is the ease with which falsehoods can be disseminated.
	6.6 PUBLICATIONS
Text-Mining: Preparing for Battle in India [In The Pipeline] The idea of the JNU collection is that no one is going to be allowed to read or download any individual papers, since that would indeed be a copyright violation for the publishers involved. Instead, the corpus as a whole will be available for machine-learning purposes to extract trends and connections – which Malamud contends is no violation at all.
The plan to mine the world’s research papers [Nature] A giant data store quietly being built in India could free vast swathes of science for computer analysis — but is it legal?
Machine-Mining the Literature [In The Pipeline] The paper today gives us a hint of what could be possible, eventually, after a lot of time, a lot of money, and a lot of (human) brainpower. Bring it on!
Blood pulls deceased star oncologist’s paper after Stanford inquiry [Retraction Watch] The journal’s move comes about a week after Retraction Watch posted a story on the previous retractions, in the Journal of Clinical Investigation (JCI), of Kohrt’s work.
	6.7.1 IA/BIOINFORMATIQUE
AI Drug Hunters Could Give Big Pharma a Run for Its Money [Bloomberg] Alphabet’s DeepMind cracked a problem that long vexed biologists, heating up a technological arms race in health care.
	6.9 CONTROVERSES
Mother wrongly diagnosed with breast cancer has double mastectomy before doctors realise their mistake [The Telegraph] Her lawyers said the mistake occurred because a biopsy sample was incorrectly recorded.
NHS cancer scans left unread for weeks because of pension row [The Guardian] “Scan report turnaround time has gone from one week to over a month. Unexpected and critical findings are going unreported for weeks. We are now just firefighting.”