Onco Actu du 12 juin 2019

	1. BIOLOGIE
SIRT1 plays key role in chronic myeloid leukemia by aiding persistence of leukemic stem cells [University of Alabama] To study those mechanisms, the UAB researchers used a CML mouse model that also has a genetic deletion of SIRT1. This allowed them to compare wild-type leukemic stem cells with SIRT1-deletion leukemic stem cells.
Unhealthy Gut Promotes Spread of Breast Cancer, Study Finds [University of Virginia] Melanie Rutkowski, PhD, of UVA’s Department of Microbiology, Immunology and Cancer Biology, found that disrupting the microbiome of mice caused hormone receptor-positive breast cancer to become more aggressive.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
FDA finalizes guidance for premarket tobacco product applications for electronic nicotine delivery systems as part of commitment to continuing a strong oversight of e-cigarettes [FDA] Under the PMTA pathway, which is the marketing pathway most likely to be pursued for ENDS products, manufacturers or importers must demonstrate to the agency, among other things, that marketing of the new tobacco product would be appropriate for the protection of the public health.
FDA unveils new guidelines for e-cigarette makers [Reuters] Currently, there are no authorized e-cigarettes on the U.S. market. The FDA, which has recently clamped down on e-cigarettes following a surge in their use among teenagers, said here the new guidelines cover issues like accidental nicotine exposure and battery safety.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
Multi-Gene Panel Testing Finds Pathogenic Variant Carriers Missed Under Current Testing Guidelines [Genome Web] As they reported in the Journal of Molecular Diagnostics today, they found pathogenic variants — and sometimes more than one pathogenic variant — in nearly 2,700 people. A portion of these individuals, though, did not meet guidelines for hereditary cancer testing.
	5.12 IMMUNOTHÉRAPIES
Maverick of cancer immunology on film [Nature] "Breakthrough" is unashamedly hagiographic, but it does make a lovely motivational film for bench scientists. There is the familiar ‘They said it couldn’t be done!’ trope, and a hefty dose of solid science triumphing over short-term business interests.
	5.12.3 IMMUNOTHÉRAPIES-COMBINAISONS
Triple Combined Therapy in BRAF-Mutated Melanoma [ESMO] The combination of immune checkpoint inhibitor with BRAF and MEK inhibition is tolerable and has promising efficacy in BRAF-mutated melanoma according to findings from three articles published on 6 June 2019 in the Nature Medicine. Such triple combination therapy warrants further investigation.
	5.12.6 IMMUNOTHÉRAPIES - AMM
Agilent Companion Diagnostic Gains Expanded FDA Approval in Head and Neck Squamous Cell Carcinoma (HNSCC) [Agilent] PD-L1 IHC 22C3 pharmDx can now be used as an aid to identify HNSCC patients for treatment with KEYTRUDA® (pembrolizumab).
FDA approves pembrolizumab for first-line treatment of head and neck squamous cell carcinoma [FDA] Approval was based on KEYNOTE-048 (NCT02358031), a randomized, multicenter, three-arm, open‑label, active‑controlled trial conducted in 882 patients with metastatic HNSCC who had not previously received systemic therapy for metastatic disease or with recurrent disease who were considered incurable by local therapies.
Merck's Keytruda, passing Opdivo, bags double head and neck cancer OK [Fierce Pharma] It also puts Keytruda ahead of archrival Opdivo from Bristol-Myers Squibb, which is cleared only for patients who have already failed on chemo—meaning those who start out on Keytruda instead of chemo won’t be eligible for Opdivo treatment later.
Merck grows Keytruda indications with head and neck cancer approval [EndPoints] As Keytruda settles into its market-leading place, bolstered by a dominant position in frontline lung cancer, Merck is busy pushing earlier uses of the PD-1 in other indications, including kidney cancer and esophageal carcinoma.
Merck's Keytruda wins FDA approval to treat head and neck cancer [Reuters] Keytruda, first approved for advanced melanoma in 2014, is Merck’s most important growth driver. It has overtaken Bristol’s Opdivo as the industry’s immuno-oncology leader with sales expected to top $10 billion this year and $20 billion in 2024, according to IBES data from Refinitiv.
FDA Approves Two New Indications for Merck’s KEYTRUDA® (pembrolizumab) [Merck] KEYTRUDA Now Approved for First-Line Treatment of Patients with Metastatic or with Unresectable, Recurrent Head and Neck Squamous Cell Carcinoma as Monotherapy for Patients Whose Tumors Express PD-L1 (CPS ≥1) or in Combination with Platinum and Fluorouracil (FU) Regardless of PD-L1 Expression.
	5.2.1 PHARMA - PARTENARIATS
J&J bags $150M option on Genmab's Darzalex successor [Fierce Biotech] J&J struck the deal on the strength of preclinical data in a panel of multiple myeloma, lymphoma and leukemia models. Genmab thinks the data provide early validation that the HexaBody technology may enable it to improve on Darzalex.
Boehringer Ingelheim and University of Dundee Highlight Successful PROTAC Drug Discovery Program and Extend Their Ongoing Anti-Cancer Alliance [Boehringer Ingelheim] PROTACs represent a new class of drug candidates with the potential to tackle compelling cancer targets which have failed traditional medicinal chemistry approaches. They work by harnessing the cell’s natural disposal system (the ubiquitin-proteasome). Candidate disease-causing proteins are labelled as “expired” proteins which the proteasome then shreds.
Genmab Signs Agreement with Janssen for Next-Generation CD38 Antibody, HexaBody®-CD38 [Genmab] Next-generation HexaBody-CD38 could potentially add to the DARZALEX multiple myeloma franchise and expand the potential of CD38-targeted therapies in further indications.
Searching for the next blockbuster to follow Darzalex, J&J finds a $150M anti-CD38 drug from partner Genmab [EndPoints] Janssen — J&J’s biotech unit — has its eyes on HexaBody-CD38, a preclinical compound generated on Genmab’s tech platform designed to make drugs more potent via hexamerization.
	5.2.3 PHARMA - ÉCONOMIE
Oncologie reels in $80M to push clinical programs, build pipeline [Fierce Biotech] Oncologie is looking to develop its programs in parallel in China and the U.S. and believes it can leverage recent regulatory changes in China to allow the use of foreign clinical trial data in new drug submissions.
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
Roche wins speedy OK for lymphoma drug Polivy [Biopharma Dive] Physicians and specialists surveyed by Cowen in March indicated they viewed Polivy as best used before CAR-T therapy as a transitional treatment, or in patients for whom CAR-T failed.
	5.4 TRAITEMENTS - ECONOMIE
Imfinzi, Opdivo among latest SMC decisions [Pharma Times] The Scottish Medicines Consortium (SMC) has announced its latest round of medicines for use by NHSScotland, publishing advice accepting five new medicines.
	5.5 ASCO
Modern-Day Cassandras: Reflections on #ASCO19 [ASCO Connection] Magnified, restored to corrugation, each descending notch on the graph represents a nameless casualty of cancer. When these declivities are understood on an individual basis, the “survival” curves become unearthed as steamrolled cemeteries. It all sounds unspeakably morbid. But without plotting the tragic data points, we have no guideposts for the still-living.
	6.1 OBSERVATION
NHS waiting times for elective and cancer treatment [Parliament.uk] Like many areas within the NHS, demand for elective and cancer treatments is growing which risks exacerbating this worsening performance. The waiting list for elective care has grown by one and a half million since March 2013 to 4.2 million in November 2018.
Most NHS trusts missing cancer targets as waiting times soar [The Telegraph] The report, published on Wednesday, warns that a key target for cancer patients to receive treatment within two months has not been hit since 2013. Last November, just 38 per cent of trusts achieved the standard.
Cancer Survivors Predicted to Number over 22 Million in U.S. by 2030 [ACS] The report uses the term “cancer survivor” to describe a person who has a history of cancer, from the time of diagnosis through the remainder of their life. However, it is important to note that many people with a history of cancer do not embrace this term.
	6.8 COMMUNICATION
Does the news reflect what we die from? [Our World in Data] Just under one-third of the deaths came from cancer; we actually google cancer a lot (37 percent of searches) and it is a popular entry here on our site; but it receives only 13-14 percent of media coverage.