Onco Actu du 30 juillet 2019

	1. BIOLOGIE
Two therapeutic targets identified for deadly lung cancer [Salk Institute] Salk Institute researchers have now discovered precisely why inactive LKB1 results in cancer development. The surprising results, published in the online version of Cancer Discovery on July 26, 2019, highlight how LBK1 communicates with two enzymes that suppress inflammation in addition to cell growth, to block tumor growth.
Cancer-cell death ironed out [Nature] Ferroptosis is a form of cell death. The finding that cells that have certain mutations in the Hippo signalling pathway are susceptible to ferroptosis might offer a way to treat a cancer called mesothelioma.
	1.4 BIOLOGIE - TECHNOS
CRISPR algorithm predicts how well gene editing will work [Stanford Medicine] "There could be quite a bit of randomness in what happens during these CRISPR edits, and that randomness can potentially create unexpected outcomes," said Zou. "So our work is motivated by whether we can quantify those odds more precisely."
	4.3 DÉP., DIAG. & PRONO. - INDUSTRIELS
Exact Sciences Touts Advantages of Genomic Health Acquisition for Pipeline Development [Genome Web] Importantly, Exact may be able to leverage Genomic Health's partnership with Biocartis to decentralize Cologuard and begin offering the test on the Biocartis Idylla instrument.
Exact Sciences to expand testing reach with $2.8B Genomic Health deal [Biopharma Dive] The Genomic Health partnership could offer Exact Sciences new relationships with oncologists. "Today, as a cancer diagnostics company, we lack an oncology sales force," Conroy said.
Diagnostic company Exact Sciences to buy Genomic Health in $2.8 billion deal [Reuters] Massaro said while the merger makes sense over time, investors may not like the deal right away due to the lack of commercial synergies. That is because Exact Sciences caters primarily to primary care physicians, while Genomic Health targets oncologists, surgeons, pathologists, and urologists, he added.
Combining to Create a Leading Global Cancer Diagnostics Company [Exact Sciences] By joining the teams at Exact Sciences and Genomic Health, we are forming a best-in-class R&D and clinical organization with enhanced scale and scope, and establishing the global infrastructure to accelerate the availability of new innovative cancer diagnostics to more patients.
As cancer detection companies thrive, Exact Sciences looks to consolidate by spending $2.8B to acquire peer Genomic Health [EndPoints] Exact Sciences’ flagship colorectal cancer test Cologuard will complement Genomic Health’s Oncotype DX, a test designed to help doctors determine the best course of treatment for women with breast cancer.
	5.10 TRAITEMENTS - ESSAIS
An Audience With Jessica Mega [Nature Reviews Drug Discovery] One benefit of this approach is that we can run more adaptive trials. We maybe won’t have to wait for the full cohort to be enrolled before we can do data analysis and look at the various outputs. And there are already some great examples of the benefits of adaptive trials.
	5.12.11 IMMUNOTHÉRAPIES - PRÉ-CLINIQUE
Could A Form of Cell Death Enhance Cancer Immunotherapy? [NCI] Because cancer cells that arise in different tissues may produce different inflammatory signals when they undergo necroptosis, the researchers are also working to understand which cytokine signals released by necroptotic cells are most important in activating an immune response in different tumors.
Researchers Discover New Combination Therapy to Treat Drug-Resistant Acute Lymphoblastic Leukemia [Case Western Reserve University] Using their mouse disease model, the researchers showed that the combination of these two treatments enhanced killing of acute lymphoblastic leukemia cells—even if the disease was advanced. Antibody and TGF-beta receptor inhibitor treatment increased natural killer cell activity against cancer cells by up to 35 percent. The researchers confirmed the combination’s efficacy in mice injected with acute lymphoblastic leukemia cells from four different patients.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
CAR T-Cell Therapy A Microcosm for the Challenges Ahead in Medicare [JAMA] While most private payers have developed policies to cover CAR T-cell therapy, few have established contracted rates with hospitals. Instead, single case agreements are negotiated for each patient meeting US Food and Drug Administration (FDA) eligibility criteria.
	5.12.5 IMMUNOTHÉRAPIES - PHARMA
Merck Data Are Another Step for Immunotherapy in Breast Cancer [Xconomy] The news is noteworthy because it marks the first time that an immunotherapy known as a checkpoint inhibitor has succeeded as a neoadjuvant treatment in breast cancer. Though checkpoint inhibitors have helped change the way a number of cancers are treated, they have had a tougher time making a similar type of impact in breast cancer.
Merck’s KEYTRUDA® (pembrolizumab) in Combination with Chemotherapy Met Primary Endpoint of Pathological Complete Response (pCR) in Pivotal Phase 3 KEYNOTE-522 Trial in Patients with Triple-Negative Breast Cancer (TNBC) [Merck] KEYTRUDA is the First Anti-PD-1 Therapy to Demonstrate a Statistically Significant Improvement in pCR Rates as Neoadjuvant Therapy for TNBC Regardless of PD-L1 Status.
$20B-plus? Merck keeps racking up PhIII successes, scoring on triple negative breast cancer challenge as analysts drive up peak sales estimates [EndPoints] As usual, we’ll have to wait for a scientific conference to see the hard numbers. But it’s important to note that Merck’s string of successes with Keytruda is also a psychological victory that can’t be underestimated.
	5.12.6 IMMUNOTHÉRAPIES - AMM
European Medicines Agency Adopts Positive Opinion for Merck’s KEYTRUDA® (pembrolizumab) in Combination with Inlyta® (axitinib) as First-Line Treatment for Advanced Renal Cell Carcinoma [Merck] Opinion Granted Based on Significant Overall Survival Benefit for KEYTRUDA in Combination with Axitinib Compared to Sunitinib in Phase 3 KEYNOTE-426 Trial.
	5.2.2 PHARMA - FUSIONS & ACQUISITIONS
Upjohn & Mylan to Merge, Freeing Pfizer to Focus on Biopharma R&D [Xconomy] Pfizer CEO Albert Bourla said spinning off Upjohn would help his company avoid the “patent cliff,” the expiration of the drug patents that keep generic competition at bay. He added that as a smaller company more focused on developing innovative new medicines, Pfizer expects revenue will be higher in five years than it would have been had the company not done the Upjohn deal.
Mylan and Upjohn, a Division of Pfizer, to Combine, Creating a New Champion for Global Health Uniquely Positioned to Fulfill the World’s Need for Medicine [Pfizer] Delivers enhanced global scale and geographic reach, including leading positions in China and other emerging markets.
Bristol-Myers Squibb Announces European Commission Approval of Pending Acquisition of Celgene [BMS] The transaction remains subject to additional customary closing conditions and other regulatory approvals. Bristol-Myers Squibb intends to close the Celgene transaction at the earliest possible date, which it currently expects to be by the end of 2019 or the beginning of 2020.
The Pfizer-Mylan deal is not quite as it appears [STAT] Since then, the company, previously not known for R&D, has done better, particularly with cancer drugs such as Ibrance for breast cancer, which was approved in 2015 and had annual sales of $4.1 billion last year. As Pfizer launches more new drugs, those other businesses represent not safety, but a drag on growth.
Pfizer's big split is finally here, thanks to a giant generics merger with Mylan [Fierce Pharma] The deal would allow Pfizer and Mylan to combine two under-pressure businesses into a new giant with projected 2020 revenues of $19 billion to $20 billion. And with that heft, it may have a better chance at weathering growing pricing pressure in the U.S. generics market.
	6. LUTTE CONTRE LES CANCERS
The patient is always right: Extracting the full value of PROMs [Pharmafile] Patient-reported outcomes measures are an invaluable tool in ensuring that the patient remains in the driving seat when it comes to their own care. But are they really hitting the mark in today’s healthcare systems?
Fighting childhood cancer with data [The Lancet] The recently validated Toronto Guidelines (a set of international staging guidelines) have shown that it is feasible to accurately stage childhood cancers from existing population registries. Such epidemiological data are essential for meaningful demographic surveillance, appropriate resource planning, and prioritisation of strategies to tackle cancer.
	6.1 OBSERVATION
The global burden of childhood and adolescent cancer in 2017: an analysis of the Global Burden of Disease Study 2017 [The Lancet Oncology] The use of DALY-based estimates is crucial in demonstrating that childhood cancer burden represents an important global cancer and child health concern.
	6.10 POLITIQUES
Wellcome Trust joins warning for no-deal Brexit, calls on Boris Johnson to cast R&D vision [EndPoints] Lady Eliza Manningham-Buller, who chairs the charity, urged Johnson to make a significant statement on science to lay out his vision in the face of global health emergencies and the looming loss of access to collaboration with European peers.
	6.7 DMP, BIG DATA & APPLIS
Is Data Sharing Caring Enough About Patient Privacy? Part II: Potential Impact on US Data Sharing Regulations [Bill of Health] Unsurprisingly such issues are also heavily discussed in other regions of the world, such as in European general policy, or in more specific health care or clinical trials transparency debates. Hence, we assume that European stakeholders will monitor the developments in Dinerstein v. Google very carefully.
	6.7.1 IA/BIOINFORMATIQUE
Artificial Intelligence Could Improve Health Care for All — Unless it Doesn’t [Undark] AI-driven medical tools could democratize health care, but some worry they could also worsen inequalities.