Onco Actu du 13 septembre 2019

	1. BIOLOGIE
Research Clears Up Mystery About Most Common Cancer Gene [Dana-Farber Cancer Institute] “When we undertook this research, we thought it would involve understanding the consequences of gain-of-function of TP53 in myeloid malignancies,” Ebert remarks. “Instead, we found an entirely different process at work. That will be critical in developing therapies for AML and MDS marked by TP53 mutations.”
How the body’s nerves become accomplices in the spread of cancer [Science] An emerging relationship between the nervous system and tumor growth suggests new therapies.
	3. PRÉVENTION
Cheap fags and booze: why now, more than ever, we need a whole government approach to health [BMJ] On Tuesday, an announcement by the Chancellor and accompanying HM Treasury tweet promoted cheap cigarettes and alcohol as something we can all look forward to following a no-deal Brexit.
	3.1 PRÉVENTION - TABAC
Pediatricians’ Offices Can Help Parents Quit Smoking, Study Shows [NCI] The study tested the effectiveness of a program called CEASE, which aims to reduce children’s exposure to secondhand smoke—and thereby improve their health—by helping parents to quit.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
A Ban on Flavored E-Cigarettes Would Sharply Cut Sales [NY Times] Companies and trade groups weigh the risks of waging a fight against a proposed ban on most flavored vaping products, to protect mint and menthol brands.
U.S. cuts vaping-related illness total under refined case definition [Reuters] The CDC defines confirmed cases as patients who developed a breathing illness after vaping and underwent extensive testing that ruled out an infection. A probable case is someone who developed a lung illness after vaping and underwent some testing.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
Drug companies pay for exclusive access to UK genetic data [Biopharma Dive] Amgen, AstraZeneca, GlaxoSmithKline, and Johnson & Johnson will each have nine months to pour over the first wave of genomic data coming out of UK Biobank before the global research community gets a chance to look at it.
	5. TRAITEMENTS
Infant with Deadly Leukemia Saved by Drug for Adult Liver Cancer [UCSF] The decision to use the drug, sorafenib, was made after pathologists identified a unique mutation in the form of two genes being fused together instead of on separate chromosomes – according to a case study publishing in the journal Leukemia . “We recommend that all patients without Ras mutations undergo RNA sequencing to identify any fusions that might be treated with targeted therapies.”
Patients With Metastatic Colorectal Cancer Harboring Certain BRAF Mutations May Respond to Anti-EGFR Therapy [AACR] BRAF mutations belong to one of three functional classes. Class 1 comprises BRAF V600 mutations. Non-V600 BRAF mutations are divided into two classes: class 2 mutations are RAS-independent, and class 3 mutations have enhanced binding to RAS and the kinase CRAF, resulting in increased RAS-dependent signaling.
Carcinogens Have Infiltrated the Generic Drug Supply in the U.S. [Bloomberg] An FDA quality-control nightmare reveals how impurities end up in America’s blood pressure pills.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
Cancer Drugs in Development May Be Targeting Wrong Proteins [The Scientist] The new findings come with caveats. In an interview with Nature, coauthor Ann Lin of Stanford University notes the study was carried out in cultured cells, leaving open the possibility “that these drug targets are essential in human patients.”
Your Cancer Targets May Not Be Real [In The Pipeline] These results also make an even stronger argument against drawing too many conclusions from RNA-level knockdown experiments in cancer cells. Many researchers have already come to similar conclusions about CRISPR experiments versus siRNA/shRNA ones based on their own experiences, but this is an excellent chapter-and-verse demonstration of just what the problems are and how deep they can run.
	5.12 IMMUNOTHÉRAPIES
Antibiotics reduce survival rates in cancer patients taking immunotherapy [Imperial College London] The team highlight some limitations to the findings, including the small number of patients, and a lack of direct observations of changes to the gut microbiome. They also add that it is not possible to account fully for the impact any other health conditions the patients may have had (comorbidities) could have had on their survival.
Antibiotic use before cancer treatment cuts survival time – study [The Guardian] In their study of nearly 200 cancer patients in two NHS hospitals, the researchers found that those who had taken broad-spectrum antibiotics for just a few days for common problems such as chest infections survived for a median of two months after immunotherapy, compared with 26 months for those who had not been on antibiotics.
	5.12.1 IMMUNOTHÉRAPIES - PARTENARIATS
University of Pennsylvania Announces Completion of Exclusive R&D Alliance With Novartis and Development of New Focused Relationship [Penn Medicine] Penn to Broaden Pathways for Development of New CAR T Cell Therapies.
	5.12.3 IMMUNOTHÉRAPIES-COMBINAISONS
Tocagen Stock Tanks After Gene Therapy Drug for Brain Cancer Fails [Xconomy] Tocagen’s approach to gene therapy aims to activate a patient’s immune system to fight cancer. Toca 511 is an injectable retrovirus. It carries genetic instructions for making an enzyme that, once in cancer cells, turns Toca FC, an antifungal compound, into what’s called 5-fluoracil, a widely used cancer drug.
Tocagen fails brain cancer test, sets about 'operational review' as shares routed [Fierce Biotech] It had been in a phase 2, but was amended and molded into a phase 3, although this did nothing to help its outcome. That year, Toca 511 was given the EMA’s PRIME designation and an FDA breakthrough tag for its phase 1 work.
In a 'make or break' moment, Tocagen falls short [Biopharma Dive] Per topline results, a combination of the biotech's immunotherapy Toca 511 and the chemotherapy Toca FC yielded a median survival time of about 11 months, one month less than the median for patients on standard treatment.
Tocagen shares collapse as investigators read last rites for PhIII brain cancer study [EndPoints] The biotech bluntly reported the failure of their pivotal Phase III study of a 2-part drug — Toca 511 & Toca FC —  for high-grade glioma. Part 1 uses a vector to attack cancer cells in the brain and deliver a gene for an enzyme, while part 2 is a prodrug — 5-fluorocytosine (5-FC) — that converts into the anti-cancer therapy 5-FU.
Tocagen Reports Results of Toca 5 Phase 3 Trial in Recurrent Brain Cancer [Tocagen] The Toca 5 Phase 3, randomized, multi-center clinical trial evaluating Toca 511 & Toca FC in patients with recurrent high grade glioma (HGG) undergoing resection missed the primary endpoint of overall survival compared to standard of care treatment (11.1 months median compared to 12.2 months, HR=1.06, p=0.6154).
Tocagen's brain cancer treatment fails late-stage study, shares crash [Reuters] Toca 511 & Toca FC, a cancer-selective therapy that spares blood cells from the common side effects associated with chemotherapy, is also being tested in bladder cancer.
	5.12.5 IMMUNOTHÉRAPIES - PHARMA
Roche's Tecentriq scores solo win in lung cancer. But can it challenge Merck's Keytruda? [Fierce Pharma] If Roche can grab an approval, Tecentriq will go up against an established player in Merck’s Keytruda, which nabbed its own monotherapy approval nearly three years ago.
Roche's Tecentriq excels in another lung cancer study [EndPoints] Roche has nine Phase III lung cancer studies underway evaluating Tecentriq as a monotherapy or in combination with other medicines across a plethora of lung cancer types.
	5.2 PHARMA
Celgene Announces Phase 3 QUAZAR® AML-001 Study of CC-486 as Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia Met Primary and Key Secondary Endpoints [Celgene] Data from QUAZAR AML-001 will be submitted to a future medical meeting.
Roche’s fixed-dose subcutaneous combination of Perjeta and Herceptin showed non-inferiority when compared to intravenous formulations for people with HER2-positive breast cancer [Roche] Results will be presented at an upcoming medical meeting.
FDA slaps a hold on one of Amgen’s early-stage cancer drugs, raising cardiac tox concerns for a top prospect in the pipeline [EndPoints] The pharma giant noted in an oncology update that their dose ranging study of the MCL1 inhibitor AMG 397 was placed on clinical hold by the agency, which prompted researchers to voluntarily halt enrollment in another early study of their other, more advanced, MCL1 program for AMG 176.
	5.2.3 PHARMA - ÉCONOMIE
Cancer drugs among US goods spared from tariffs as China issues first exemptions in trade war [EndPoints] While the exemptions signal goodwill from Beijing, it’s unlikely to have a big impact on pharma players’ plans in the country as they shift their focus from old drugs near the end of their patent life to innovative treatments, which are getting to market more quickly thanks to dramatic reforms.
	6. LUTTE CONTRE LES CANCERS
After nearly dying five times, a young doctor learned to treat himself. Now he wants to help others with rare disease [STAT] Dr. David Fajgenbaum has nearly died not once, but five times. The cause each time was a rare disorder called Castleman disease, an affliction on the boundary between cancer and an autoimmune disorder.
	6.1 OBSERVATION
UK cancer survival rates are too low – our priorities are all wrong [The Guardian] Experts who have studied possible reasons for worse performance in the UK have concluded that it may have more to do with subtle everyday behaviours of doctors and patients that influence how fast diagnoses can be made.
	6.11 PATIENTS
Cancer patients use crowdfunding for medical bills, expenses [Reuters] To get a sense of the types of expenses for which cancer patients were seeking help, Breyer and colleagues searched in October 2018 on the GoFundMe website for mentions of the 20 most common cancers in the U.S. They identified 37,344 campaigns and selected a random sample of 1,035 for detailed analysis.
	6.12 ETHIQUE
Cancer researchers’ failure to disclose industry payments damages patient trust — and care [STAT] The establishment of a centralized database for clinicians’ financial disclosures would do much to restore trust in the often-criticized medical field.
	6.9 CONTROVERSES
MSK picks brain cancer expert Lisa DeAngelis as its next CMO — following José Baselga’s controversial exit [EndPoints] DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.