Onco Actu du 23 juillet 2018

	1. Biologie
Leukaemia follows a blood-vessel track to enter the nervous system [Nature] Certain cancers are prone to invade the nervous system, which leads to poorer prognosis. A study of leukaemia in mice reveals an unexpectedly direct invasion route from the bone marrow to the central nervous system.
	1.1 Biologie - Gènes
A Close Look at a Cancer Genome [In the Pipeline] Note that in these cells HER2 has been translocated into chromosome 8 from its original home on chromosome 17 and then copied “dozens of times” with more translocations. We’re seeing the result of a long series of bad events piled up on each other. To paraphrase Adam Smith, there is a lot of ruin in a cell.
	1.4 Biologie - Technos
Potential DNA damage from CRISPR has been ‘seriously underestimated,’ study finds [STAT] Nature Biotechnology took a year to publish the paper, after asking Bradley numerous variations of “are you sure?” and “did you consider this?” and asking him to run additional experiments, Bradley said. The results all held up.
The safety of CRISPR-Cas9 gene editing is being debated [The Economist] A study shows problems, but they are surmountable.
CRISPR gene editing produces unwanted DNA deletions [Nature] DNA-cutting enzyme used for genetic modification can create large deletions and shuffle genes.
	2. Etiologie
Contagious cancer could have wiped out America's first dogs [Nature] Canine transmissible venereal tumour (CTVT) is one of a handful of known contagious cancers — more famous are the two forms that threaten Tasmanian devils with extinction.
	2.4 Etiologie - Portables, ondes e-m
Mobile phones and cancer – the full picture [The Guardian] An article we published last week about links between mobiles and cancer proved highly controversial. Here a cancer expert and physicist argues that it misrepresented the research and that fears are ill-founded.
	2.6 Etiologie - Environnement
The man who haunts Europe’s food safety watchdog [Politico] “EFSA respects the right of any individual to express his or her personal views regarding its scientific conclusions,” the spokesperson said. “We also believe that for the sake of transparency any relevant interest should be declared when expressing a view or initiating a campaign, something that Professor Portier admittedly failed to do when signing this letter.”
UK accused of 'green Brexit hypocrisy' over regulation of suspected carcinogen [The Guardian] UK attempted to weaken new EU regulations of a lucrative whitening chemical, Ti02, found in cosmetics and sunscreens.
EPA Stalls Release of Carcinogen Report [The Scientist] An investigation by Politico finds the agency has been sitting on an assessment of formaldehyde’s cancer risks for a year and a half.
	3. Prévention
How to Minimize Pancreatic Cancer Risk [NY Times] Obesity, Type 2 diabetes and metabolic syndrome, all of which have risen to epidemic levels in recent years, are linked to pancreatic cancer.
	3.3 Prévention - Vaccins
Boys should be given HPV jab, says vaccine committee. Here’s what happens next. [Cancer Research UK] The next step is for the Government to formally accept the recommendation and extend the programme to boys. Until it does, we won’t know the details of when and how the programme will be rolled out. Once they have accepted the recommendation, the Government must publish a plan and timetable for the roll-out.
HPV vaccination for males: effective and safe [BMC Blog] Research has proven the benefits of vaccinating girls against HPV prior to sexual debut. But could the vaccine also benefit boys? The authors of a new article published in BMC Medicine conducted a systematic review to find out. Their results have caused reverberations in the medical community, already prompting one major European country to update its vaccination recommendations.
JCVI statement: extending the HPV vaccination programme – conclusions [Gov.uk] Conclusions on extending the human papillomavirus infection (HPV) vaccination programme to adolescent boys in the UK.
	3.8 Prévention - Alimentation
Low- or no-calorie soft drinks linked to improved outcomes in colon cancer [Yale News] “Artificially sweetened drinks have a checkered reputation in the public because of purported health risks that have never really been documented,” said the study’s senior author, Charles S. Fuchs, M.D., director of Yale Cancer Center. “Our study clearly shows they help avoid cancer recurrence and death in patients who have been treated for advanced colon cancer, and that is an exciting finding.”
Diet soda and colon cancer: What you need to know [HealthNewsReview] This is an observational study suggesting that colon cancer patients who regularly drink diet soda have a lower risk of their tumors coming back, or of dying from their cancer. With this type of study it’s inaccurate and misleading to imply this is a cause-and-effect relationship.
	4.12 Biopsies liquides
Liquid Biopsy Controversy Rages On [Forbes] More comprehensive studies with larger numbers of patients, building on the original study from Johns Hopkins are certainly warranted to ensure these liquid biopsies are standing up to scrutiny. However, perhaps more importantly, the subjective nature of interpreting these tests is simply not compatible with the current marketing approach.
A Blood Test For Early Detection Of Melanoma? Not Yet [Dr. Len] The research is far from being shown to have proven value in the early diagnosis of melanoma, a less common but certainly potentially deadly form of skin cancer. I am not certain the various media headlines and articles appropriately reflected that fact, once again offering hype over inconvenient reality.
Magnetized wire could be used to detect cancer in people [Stanford Medicine] Scientists at Stanford used the wire to capture free-floating tumor cells in the blood, a technique that soon could be used in humans to yield an earlier cancer diagnosis.
Stanford promotes a magnetized wire ‘to detect cancer in people.’ What you need to know [HealthNewsReview] Compelling as that possibility may be, it’s premature to project such human applications from this proof-of-concept study in pigs.
Why Consistent Testing Methods Are Crucial for Liquid Biopsies [University of Michigan] A new study helps set standards for RNA sequencing, improving standard practice and laying the foundation to move the field forward.
	4.2 Dép., diag. & prono. - Génome
Double Jeopardy: Gene-Sequencing Test Uncovers New Clues about a Defect Seen in Many Tumors [Memorial Sloan Kettering Cancer Center] MSK-IMPACT™ has led to many important findings about cancer genomics. In a recent study, researchers found that a genetic state in tumors called whole-genome doubling is connected with worse outcomes for people with cancer.
	4.9 Dép., diag. & prono. - Sein
New approach to breast cancer screening — tailoring guidelines for each patient — may save lives and money, study says [STAT] The researchers ran computer simulations on a hypothetical cohort of over 360,000 women to test the efficacy and costs of risk-stratified screening. They took data from the National Health Services Breast Screening Program in the U.K. to model outcomes.
Computer simulation suggests risk-based breast screening could have benefits [Cancer Research UK] Professor Fiona Gilbert, a co-author of the study from the University of Cambridge, said: “We need to change the model of delivery of breast screening and recognise that women are individuals with different risks and lifestyles. They should be offered screening tailored to their own profile.”
No screening is better for women with low breast cancer risk, finds study [The Guardian] In the risk-stratified group, among those who were not screened, there were 27% fewer over-diagnoses, 3% fewer breast cancer deaths avoided, and the NHS cost was reduced by £20,000. In the high risk 70%, there were 71% fewer over-diagnoses, 10% fewer breast cancer deaths avoided, and the NHS cost was £538,000 less.
Many Breast Cancer Patients Don’t Get Recommended Follow-Up, Study Finds [Wall Street Journal] Practices vary widely, with some women not getting recommended mammograms while others undergo unnecessary scans.
	5. Traitements
Prostate cancer ultrasound treatment as effective as surgery or radiotherapy [Imperial College London] A new study, carried out at six hospitals across the UK, tracked 625 men with prostate cancer who received a type of treatment called high-intensity focused ultrasound (HIFU). The research, published in the journal European urology, is the largest ever study of HIFU treatment used to target prostate tumours.
Top oncologist to study effect of diet on cancer drugs [The Guardian] Siddhartha Mukherjee says trial is first in a series on ‘rethinking human diets for cancer’.
	5.1 Traitements - Pré-clinique
Overcoming resistance to a standard chemotherapy drug [Emory] In animal models with implanted tumors, cisplatin could be combined with lestaurtinib against several cancer cell types: head and neck squamous cell, lung cancer, ovarian, and cervical carcinoma.
Mouse Study Links Immune Cells to Diarrhea Caused by Chemotherapy [NCI] The Washington University researchers found that macrophages were part of a previously unknown signaling pathway that participates in controlling the activity of smooth muscle cells in the gastrointestinal (GI) tract.
	5.12 Immunothérapies
Can Age Affect Response to Immune Checkpoint Inhibitors? [NCI] The findings suggest that cytotoxic T cell activity is suppressed by regulatory T cells in melanoma tumors of younger patients, the researchers wrote, limiting the effectiveness of immune checkpoint inhibitors.
	5.12.1 Immunothérapies - partenariats
Number 7? Celgene partner BeiGene joins the crowd with stellar PD-1/L1 data from a pivotal test [EndPoints] BeiGene announced just ahead of the start of the week in Beijing that their PD-1 tislelizumab — partnered with Celgene — scored stellar data in a small Phase II trial for classical Hodgkin’s lymphoma among patients who had either failed or couldn’t take autologous stem cell transplantation.
	5.12.2 Immunothérapies - CAR-T, thérapies cellulaires
Natural Killer Cells Prove Effective as a CAR Therapy in Mice [The Scientist] Stem-cell–derived natural killer cells engineered in a similar way to CAR-T cells may pave the way to “off the shelf” cancer therapies that aren’t patient-specific.
Swift Gene-Editing Method May Revolutionize Treatments for Cancer and Infectious Diseases [NY Times] In the new study, Dr. Marson and his colleagues engineered T-cells to recognize human melanoma cells. In mice carrying the human cancer cells, the modified T-cells went right to the cancer, attacking it.
	5.12.3 Immunothérapies-combinaisons
FDA grants Breakthrough Therapy Designation for Roche’s Tecentriq in combination with Avastin as first-line treatment for advanced or metastatic hepatocellular carcinoma (HCC) [Roche] The designation is based on data from a Phase Ib study assessing the safety and clinical activity of the combination of Tecentriq and Avastin.
	5.12.5 Immunothérapies - Pharma
Roche’s Tecentriq in combination with pemetrexed and platinum-based chemotherapy reduced the risk of disease worsening or death in the initial treatment of people with advanced lung cancer [Roche] While a numerical improvement for the co-primary endpoint of overall survival (OS) was observed, statistical significance was not met at this interim analysis, and the study will continue as planned with final OS results expected next year.
Roche takes Tecentriq hit on survival data [Reuters] In contrast, Merck’s Keynote-189 study demonstrated its Keytruda plus chemotherapy improved survival in newly-diagnosed patients. That leaves Tecentriq, with sales just a fraction of Keytruda’s and Bristol-Myers Squibb’s Opdivo, an also-ran in the battle for supremacy against lung cancer, the disease’s most-lucrative market.
Hitting cancer early: AstraZeneca's bid to outmaneuver rivals [Reuters] The idea that immunotherapy may actually work best in less sick patients is logical, since the immune system’s natural role is to destroy nascent tumors. Indeed, some cancer doctors believe this could become the main battleground in future.
	5.12.6 Immunothérapies - AMM
Bristol-Myers Squibb’s Opdivo ® (nivolumab) + Low-Dose Yervoy ® (ipilimumab) is the First Immuno-Oncology Combination Approved for MSI-H/dMMR mCRC Patients Who Progressed Following Treatment with a Fluoropyrimidine, Oxaliplatin and Irinotecan [BMS] Opdivo + Yervoy is now approved in three tumor types, dosing and administration varies by tumor.
	5.12.8 Immunothérapies - Economie
CMS Abandonment of Outcomes-Based Payment Deal with Novartis is a Missed Opportunity [Harvard Law Blog] Its decision to abandon the agreement in secret, however, is a serious missed opportunity for the administration. CMS could have taken this opportunity to admit its mistakes, both substantively and procedurally, and to improve this deal or ensure it uses a more appropriate process for others going forward.
Staggering Prices Slow Insurers’ Coverage Of CAR-T Cancer Therapy [KHN] Last spring, Medicare announced payment rates for providers who administer Yescarta and Kymriah on an outpatient basis. The problem with this plan: Facilities typically provide treatment on an inpatient basis, because of the potential for severe, systemic side effects.
	5.2 Pharma
Phase 3 Trial of NINLARO® (ixazomib) as Maintenance Therapy Met Primary Endpoint Demonstrating Statistically Significant Improvement in Progression-Free Survival in Patients with Multiple Myeloma Post-Transplant [Takeda] There were no new safety signals found in TOURMALINE-MM3. The safety profile of NINLARO in the maintenance setting is consistent with previously reported results of single-agent NINLARO use. Full data results will be submitted for presentation at the 60th American Society of Hematology Annual Meeting in December.
Janssen Provides Update on IMBRUVICA® (ibrutinib) Phase 3 PHOENIX Trial in Newly Diagnosed Non-Germinal Center B Cell (Non-GCB) Subtype of Diffuse Large B-Cell Lymphoma (DLBCL) [Janssen] "While we are disappointed that the overall study did not result in the outcome that we had hoped for in patients living with DLBCL, we are conducting additional analyses to further understand potential benefits we have observed in a sub-population of patients."
CTI Biopharma's cancer drug fails late-stage trial, shares tumble [Reuters] The drug, Pixuvri, did not show improvement in the length of time patients survived without any progression in the disease. CTI’s treatment was being tested in combination with Roche Holding’s Rituxan in patients with aggressive B-cell Non-Hodgkin lymphoma.
Mersana's cancer drug trial put on hold by FDA; shares halted [Reuters] The experimental treatment is being tested in patients whose advanced tumors express a protein called HER2, including those with cancers of the breast, lung and stomach.
	5.2.1 Pharma - Partenariats
Novartis punts a late-stage PI3K drug with a worrying safety profile to one of China’s upstart biotechs [EndPoints] Late last year a group of scientists published a report in The Lancet — funded by Novartis — that concluded the drug’s safety profile “does not support its further development” in breast cancer.
	5.3 Traitements - FDA, EMA, NICE...
EMA identifies gaps in industry preparedness for Brexit [EMA] Survey indicates that some companies need to step up efforts to ensure medicine supply in the EU.
EU drug regulators step up work to prepare for 'no deal' Brexit [Reuters] Although the UK’s exit from the European Union is still eight months away, Britain has already stopped taking on new projects that will extend beyond March 29, 2019 and is preparing to hand over existing drug review work to other countries.
FDA’s revolving door: Companies often hire agency staffers who managed their successful drug reviews [Science] "When your No. 1, major employer after you leave your job is sitting across the table from you, you're not going to be a hard-ass when you regulate. That's just human nature."
	5.3.4 Traitements - AMM (FDA, EMA,...)
U.S. FDA Approves XTANDI® (enzalutamide) for the Treatment of Men with Non-Metastatic Castration-Resistant Prostate Cancer (CRPC) [Pfizer] First and Only Oral Treatment FDA-Approved for Both Non-Metastatic and Metastatic CRPC.
FDA approves first cancer drug through new oncology review pilot that enables greater development efficiency [FDA] This is the first approval that FDA has granted as a part of two new pilot programs announced earlier this year that collectively aim to make the development and review of cancer drugs more efficient, while improving FDA’s rigorous standard for evaluating efficacy and safety.
European Commission Approves Expanded Indication for Sprycel (dasatinib) to Include Treatment of Children with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase [BMS] Approval includes the first powder for oral suspension formulation of a tyrosine kinase inhibitor developed for administration in pediatric patients.
Agios scores its second new drug approval, ivosidenib heads to the AML market [EndPoints] The new drug will be marketed by Agios as Tibsovo, and the company is charging $26,115 for a one-month supply.
FDA approves ivosidenib for relapsed or refractory acute myeloid leukemia [FDA] Approval was based on an open-label, single-arm, multicenter clinical trial (AG120-C-001, NCT02074839) that included 174 adult patients with relapsed or refractory AML with an IDH1 mutation confirmed using the Abbott RealTime IDH1 Assay, the FDA-approved test for selection of patients with AML for treatment with ivosidenib.
	5.4 Traitements - Economie
Cancer drug for children recommended after becoming cost effective for NHS patients [NICE] Around 60% of children with high-risk neuroblastoma could be treated with dinutuximab beta.
Life-extending immunotherapy approved on NHS for children with neuroblastoma [Cancer Research UK] Previously, NICE said dinutuximab beta was too expensive for use on the NHS. But an agreement was reached with the pharmaceutical company who make the drug, so it could be made available at a discounted price.
More people to be given dye to highlight brain tumours to surgeons say NICE [NICE] Hundreds of patients a year set to benefit from roll out of dye to all of England’s neurosurgical units.
Brain tumour chemotherapy now available to even more NHS patients [Cancer Research UK] “This is a practice-changing trial,” says Dr Sara Erridge, a Cancer Research UK-funded scientist at the University of Edinburgh, who led the UK arm of the international CATNON (BR14) study. “Temozolomide has now been introduced to be part of the standard of care for this group of patients.”
	6. Lutte contre les cancers
NIH and Prostate Cancer Foundation launch large study on aggressive prostate cancer in African-American men [NCI] The $26.5 million study is called RESPOND, or Research on Prostate Cancer in Men of African Ancestry: Defining the Roles of Genetics, Tumor Markers, and Social Stress.
Cancer drug movie strikes nerve in China, becomes box-office hit [Reuters] A low-budget Chinese movie about a leukemia patient who turns to smuggling cheaper cancer drugs from India has struck a chord with Internet users and even the country’s leaders, spotlighting national anxieties about unaffordable hospital care.
A 6-year-old was diagnosed with an aggressive brain tumor. Then her little brother was, too. [Washington Post] Javahery said Kalea and Noah's tumors, which measured 3.5 cm and 5 cm, respectively, are being tested for gene mutations to help determine what may have caused them. The two children as well as their parents may also undergo genetic testing, he said.
	6.1 Observation
Diabetic women at greater risk of cancer than men, according to new study [The Telegraph] A review of 47 studies involving almost 20 million people has shown for the first time that women with the condition are at a greater risk than men of developing any form of the disease, the authors said. They warned the gender differences were "not insignificant" and needed addressing.
Toward the control of cancer [CA: A Cancer Journal for Clinicians] These articles summarize where we have come from, the current state of cancer in the United States, and how more consistent and equitable application of currently available interventions can further reduce the cancer incidence and death rates. When there are sufficient data to make a projection, estimates of the potential effect of cancer control interventions are included.
	6.10 Politiques
It’s time to burst the biomedical bubble in UK research [The Guardian] A new study calls for a rebalancing of research and innovation funding to better meet the UK’s economic, social and health needs.
Leading International Cancer Organizations Call on United Nations Members to Reduce Disease Burden [ASCO] In the statement, ASCO and ESMO reiterate their support for the WHO’s goals of reducing premature mortality from cancer by 25% by 2025, and by 33% by 2030.
	6.10.1 Politiques (USA)
Merck Is Lowering Drug Prices. There’s a Catch. [NY Times] Merck’s action shows just how cautiously the industry is shifting strategies: It did not cut the prices of any blockbusters like the cancer treatment Keytruda or the diabetes drug Januvia.
Unpacking the bold — and the bluster — in Trump’s plan to bring down drug prices [STAT] The boldest — and most politically surprising — proposal from the Trump administration centers on an idea long favored by the left, and long and staunchly opposed by drug makers: importing drugs from other countries.
Merck lowers prices of some drugs after Trump calls out industry [Reuters] In addition to slashing the price of Zepatier, which owns a very small share of the hepatitis market, Merck said it would lower the list price by 10 percent of six other older drugs with minuscule sales.
Many Drugmakers Ignore Trump—and Raise Prices Anyway [Bloomberg] This month, Roche Holding AG boosted the price of a single-use vial of breast-cancer drug Herceptin by 3 percent. Avastin, another cancer drug, went up 2.5 percent.
Pfizer’s Announces it Will Defer Company’s Price Increases [Pfizer] “Pfizer shares the President’s concern for patients and commitment to providing affordable access to the medicines they need,” said Ian Read. “
Trump Phones, And Pfizer Reverses Price Hikes. But Why? [Forbes] Waiting six months isn't huge hardship. It's important that the Pfizer concession comes with a real deadline: If the system has not changed come New Year's, those price increases will go back into effect.
	6.12 Ethique
If you give your DNA and tissues to science, should you get a peek at what they might contain? [Science] A huge hurdle, however, is that the research enterprise isn’t well set up for returning many results. Doing so can be a burden for research groups, both logistically and in terms of cost. And the regulations governing return are convoluted and confusing.
	6.3 Associations/Fondations
Biomedical charity places major bet on ‘bold’ research to win bigger payoffs [Science] The London-based Wellcome Trust, announced this week that it would put £250 million (about $330 million) toward pursuing “bold ideas that would fall outside the remit of conventional life sciences funding.” The money is earmarked for ideas that have a high risk of failing or “need to overcome a major scientific or technical hurdle.” The money will also be open to researchers without a background in life sciences.
	6.5 Médecines alternatives
Mixing complementary therapy with standard cancer treatment could affect survival [Cancer Research UK] Patients have the right to make their own decisions about treatment, but that should come with clear information on what the impact of that decision might be. This study helps make part of that story clearer.
Alternative medicine kills cancer patients, “complementary” edition [Science-Based Medicine] It is not surprising that cancer patients who choose alternative medicine have a higher risk of dying from their cancer. A followup study to one done last year expands upon previous findings and comes to the same conclusion yet again.
Cancer patients who choose complementary medicine are twice as likely to die within seven years, study suggests [The Telegraph] Researchers from Yale University followed 1,290 patients who were diagnosed with breast, prostate, lung, or colorectal cancer between 2004 and 2013. Of those, they found 258 used complementary medicine and 1,032 used conventional therapies.
	6.6 Publications
Dutch publishing giant cuts off researchers in Germany and Sweden [Nature] Negotiations with Elsevier have stalled over open-access deals.
Universities in Germany and Sweden Lose Access to Elsevier Journals [The Scientist] While Elsevier’s papers remain inaccessible, academics are turning to alternative means of obtaining them, such as using inter-library loan services, emailing authors, finding earlier versions on preprint servers, or buying individual papers.
	6.7.2 Applis
Mobile Health Apps Get An FDA Push [Fortune] And while there are clearly some issues that need more creative thinking and resolution—notably, cybersecurity—the FDA does seem to be creating a regulatory framework that will encourage progress in digital health, not quash it.
	6.9 Controverses
Pharma banks on cancer patients who are ‘determined to keep fighting’ [HealthNewsReview] Patients, family members and doctors all need to understand it’s not just about choosing treatment wisely, he said, but avoiding treatment wisely too.
Foundation misleads vulnerable cancer patients with clickbait diet advice [HealthNewsReview] Beyond the outrage expressed in these tweets is the fact that this misinformation is being spread by a blogging cancer researcher, on the website of an organization that raises funds for what is otherwise a publicly funded, provincial health care provider whose mission is to address incidence, mortality, and quality of life issues of cancer.
Top cancer genetics professor quits job over bullying allegations [The Guardian] Nazneen Rahman will leave the ICR in October after harassment claims.