Onco Actu du 6 décembre 2018

	1. Biologie
Cancer researchers seek to harness mysterious DNA ‘super-enhancers’ [Nature] Whether DNA segments that amplify gene activity represent a previously unrecognized form of gene regulation is still under debate.
	1.4 Biologie - Technos
CRISPR Scientists Slam Methods Used on Gene-Edited Babies [The Scientist] Instead of producing a 32-base-pair deletion, He created entirely different mutations in the babies’ DNA: One of the twins—whom He calls Lulu—has a 15-base-pair deletion, while Nana has a four-base-pair deletion.
	3.3 Prévention - Vaccins
Quebec’s change to HPV vaccine program divides experts [The Globe and Mail] Under the new program, which started this fall, students receive one shot of Gardasil 9, which protects against nine strains of HPV, including 16 and 18, the two that cause the majority of cervical, anal and other HPV-related cancers. Early next year, students will receive a shot of Cervarix, which protects against HPV 16 and 18 only.
	4.12 Biopsies liquides
Using water and gold, Australian researchers discover ‘universal cancer biomarker’ [FierceBiotech] It has shown to be up to 90% accurate in tests of 200 human cancer samples and normal DNA, they said, though it has not been tested in a clinical trial. Their research was published in the journal Nature Communications.
Holy grail cancer test? Hold on. Here’s what you need to know [HealthNewsReview] I have often said that anytime you hear about a “simple cancer test,” run for the hills because there’s no such thing. This researcher may be referring to the technology, but the application of that technology – the leap from lab to bedside – brings with it many levels of complexity.
New Universal Cancer Test Takes Only Ten Minutes. The Secret Ingredient? Gold. [Forbes] The new technology has shown a reasonable level of accuracy in discriminating between healthy and cancerous cells in initial tests, but much more work to refine this needs to be done before the test can be relied upon. "Just how useful this test will be for routine clinical use will depend on extensive testing in the general population to see how often it gets things wrong," said Chakravarthy.
‘Universal fingerprint’ in cancer DNA points to potential blood test. But it’s not ready for patients [Cancer Research UK] “Often these tests get overhyped very early on in their development, which can be extremely unhelpful,” says Pharoah. “It’s a long road from discovering a new technology to actually having something that could benefit patients, and this test is right at the start of that journey.”
Grail Launches New Early Cancer Detection Study, Refocuses Strategy to Multi-Cancer Test [Genome Web] While the Summit study is focused on individuals at risk for lung cancer, the data will be used to further develop Grail's multi-cancer cell-free DNA sequencing test, not a separate lung cancer-focused test.
	4.2 Dép., diag. & prono. - Génome
The UK has sequenced 100,000 whole genomes in the NHS [Genomics England] Pioneering 100,000 Genomes Project reaches its goal and thanks all involved.
	5.1 Traitements - Pré-clinique
Mannose and Cancer [In the Pipeline] The paper shows that mice with an induced colon-cancer phenotype have significantly fewer tumors when their water supply is supplemented with mannose, and there seemed to be no ill effects from the treatment.
	5.10 Traitements - Essais
Phase 3 Trial of Rova-T as Second-line Therapy for Advanced Small-Cell Lung Cancer (TAHOE Study) Halted [AbbVie] Independent Data Monitoring Committee responsible for ongoing review of study data recommended enrollment be stopped.
AbbVie’s troubled $10B Rova-T cancer drug program takes a sudden turn toward the cliff [EndPoints] Researchers slammed the brakes on one of their Phase III studies of the $10 billion drug after an independent group of monitors determined that their drug was linked to a shorter overall survival rate than the chemo drug used in the control arm.
AbbVie halts late-stage trial for lung cancer drug Rova-T [Reuters] AbbVie acquired Rova-T through its $5.8 billion acquisition of Stemcentrx in 2016, as the company aimed to enter the broad and lucrative arena of solid tumors and lessen dependence on its arthritis treatment Humira, the world’s top selling drug.
	5.12 Immunothérapies
A minor population of tumor infiltrating CD8+ T cells actually express tumor antigen specific TCR [NIHilist's Immunology] In summary, this study tried to show [but utterly failed in my view] that for some tumors tumor-reactive TCRs among TILs are quite rare. What are then such TILs' TCR specificity are unknown. Why are they recruited in tumor tissue is not known either.
	5.12.2 Immunothérapies - CAR-T, thérapies cellulaires
In CAR-T, manufacturing a hurdle Novartis has yet to clear [BiopharmaDive] About eight months on from securing a second approval for Kymriah (tisagenlecleucel), the company is still delivering the CAR-T treatment to some patients for free, unable to charge for a product that — while OK for use in patients — doesn't meet stricter specifications established for commercial use.
	5.2 Pharma
AstraZeneca's Calquence found success in lymphoma. Will CLL follow? [FiercePharma] “When we speak with clinicians, their real-world experience with the efficacy and the side effects associated with Calquence is really positive. We hear physicians talk about how they get fewer calls from patients. … That makes it a drug that for them, they’re finding pretty easy to manage.”
	5.7.1 SABCS-communiqués
Roche’s Kadcyla cut the risk of disease recurring by half compared to Herceptin in people with HER2-positive early breast cancer with residual disease after neoadjuvant treatment [Roche] At three years, 88.3% of people treated with Kadcyla in the adjuvant HER2-positive early breast cancer setting did not have their breast cancer return compared to 77.0% treated with Herceptin, an 11.3% improvement.
	5.7.3 SABCS-AACR
Delaying Adjuvant Chemotherapy Associated With Worse Outcomes for Patients With Triple-negative Breast Cancer [AACR] Morante and colleagues found that patients who delayed starting adjuvant chemotherapy for more than 30 days after surgery had a more than 90 percent increased risk for disease recurrence and death compared with those who started the treatment in the first 30 days after surgery.
Adjuvant Chemotherapy Might Not Add Benefit in Breast Cancer Patients who Have Excellent Response to Neoadjuvant Chemotherapy [AACR] The team conducted a PubMed search and identified eligible clinical trials from 1999 to 2016. Of the 3,209 abstracts reviewed, 27,895 patients from 52 studies met inclusion criteria.
Adjuvant Capecitabine Did Not Significantly Improve Outcomes for Patients With Early-stage Triple-negative Breast Cancer [AACR] Subgroup analysis suggested the treatment may benefit patients with nonbasal-like disease.
Phase III KATHERINE Clinical Trial Crossed Early Reporting Boundary and Met its Primary Endpoint [AACR] Adjuvant T-DM1 improved invasive disease-free survival (IDFS) in patients with HER2-positive early breast cancer with residual invasive disease at surgery following neoadjuvant chemotherapy and trastuzumab.
	5.8 ASH
At ASH, bispecific cancer therapies make a mark [BiopharmaDive] So-called bispecifics, by contrast, simultaneously lock onto antigens expressed by both tumor and immune cells, seeking to bring the two together in a lethal marriage for the cancer. In this way, bispecifics act as a kind of guide for the immune system, activating and chaperoning the T cell to attack the tumor.
3 questions leaving ASH [BiopharmaDive] Has Celgene proved its pipeline? What to do when CAR-T patients relapse? Which technology will prove its edge in blood cancers?
	5.8.4 ASH - CAR T
Mayo Clinic researchers identify new strategies that may improve CAR-T cell therapy [Mayo Clinic] The strategy involves blocking the GM-CSF protein, which is produced by CAR-T cells and other cells using a clinical-grade antibody (lenzilumab).
	5.8.6 ASH - Leucémies
Potential seen to tailor acute myeloid leukemia treatment [UW Medicine] The researchers found that leukemia stem cells and blast cells diverged in their drug susceptibility patterns, and also that these patterns differed from patient to patient.
Ibrutinib plus rituximab superior to standard treatment for some patients with chronic leukemia [NCI] The data and safety monitoring board overseeing the trial, known as E1912, recommended that these results be released immediately given their significance to public health.
	6.6 Publications
Plan S: Impact on Society Publishers [The Scholarly Kitchen] While in theory Plan S supports “diversity of models and non article processing charge (APC)-based outlets,” in reality such models (other than the hybrid model which Plan S seeks to eliminate) are not presently available to society publishers. How is a society to continue to operate its journals with no subscription revenues, no permission and reprints revenues, and no APC revenues?
	6.7 DMP, Big Data & applis
U.K. sets out digital, data-driven plan to accelerate R&D [FierceBiotech] The U.K. government has set out how it plans to use data and digital technologies to attract clinical trials. Near-term plans include the creation of a system for assessing study feasibility and an app to connect patients to studies.
	6.9 Controverses
How sure are you of your result? Put a number on it [Nature] Let’s require that any researcher making a claim in a study accompany it with their estimate of the chance that the claim is true — I call this a confidence index. As well as, “This drug is associated with elevated risk of a heart attack, relative risk (RR) = 2.4, P = 0.03,” investigators might add: “There is an 80% chance that this drug raises the risk, and a 60% chance that the risk is at least doubled.”