Onco Actu du 8 octobre 2019

	1. BIOLOGIE
Lung Cancer Studies From TRACERx Consortium Explore How Tumor Cells Evolve [Genome Web] The researchers developed a 23-gene prognostic signature they called the outcome risk-associated clonal lung expression (ORACLE) biomarker that they said avoids the issue of heterogeneity by relying on stable genetic features. They reported that patients with a low-risk ORACLE signature had a higher three-year overall survival rate, as compared to those with a high-risk signature
Secrets of lung cancer spread found in patients' blood and biopsies [Cancer Research UK] Together, the new findings provide clues as to which patients could be safely treated with milder therapies, such as surgery alone, and which may need additional treatments including chemotherapy.
	1.1 BIOLOGIE - GÉNOME
Prostate Cancer Methylation Levels Linked to Regulatory Variants in Germline [Genome Web] Members of an international team led by investigators in Canada, the US, and the UK brought together new and already available whole-genome or exome sequence data for nearly 600 individuals with localized prostate cancer to tally germline variants across the genome. They then looked at how these alterations lined up with somatic mutations and array-based DNA methylation features in the patients' tumor tissue.
	1.3 PRIX NOBEL
Three scientists win Nobel Prize in medicine for discovering how cells sense and adapt to oxygen levels [STAT] Kaelin is a co-founder of Cambridge, Mass.-based biotech Tango Therapeutics, which develops molecularly-targeted cancer drugs, as well as Cedilla Therapeutics, which is developing drugs to treat cancer by targeting tumor-driving proteins.
Nobel Prize in medicine goes to oxygen sensing research [Fierce Biotech] That broad potential is reflected in the pipeline of drugs targeting pathways related to the research. Companies including AstraZeneca see inhibitors of HIF-prolyl hydroxylase as a better way to treat renal anemia, while Merck illustrated the excitement about the potential of the research in cancer by paying $1.05 billion upfront to buy Peloton Therapeutics for its HIF-2α inhibitor.
Nobel Prize in Medicine Awarded for Research on How Cells Manage Oxygen [NY Times] The discoveries reveal the cellular mechanisms that control such things as adaptation to high altitudes and how cancer cells manage to hijack oxygen.
Trio wins Nobel Prize for Medicine for 'fundamental' discovery [EndPoints] Compared to last year — when James Allison and Tasuku Honjo won for pioneering cancer immunotherapies that have already been used to treat thousands of patients – this year’s’ work feels academic in its impact to-date on medicine and pharmacology. But it comes from winners who have pushed back on translatability as a counterproductive metric for research.
Nobel prize in medicine awarded to hypoxia researchers [The Guardian] The work has led to the development of a number of drugs such as roxadustat and daprodustat, which treat anaemia/ Similar drugs aim to help heart disease and lung cancer patients who struggle to get enough oxygen into their bloodstream. More experimental drugs based on the finding seek to prevent other cancers growing by blocking their ability to make new blood vessels.
Biologists who decoded how cells sense oxygen win medicine Nobel [Nature] Kaelin, in particular, has taken his field to task for pursuing possible cancer treatments that aren’t backed up by strong evidence. “The most dangerous result in science is the one you were hoping for, because you declare victory and get lazy,” he told scientists at a 2018 talk at the US National Institutes of Health in Bethesda, Maryland.
The 2019 Medicine Nobel [In The Pipeline] This also allows you to see how tumor biology ties into the HIF story, since solid tumors are almost invariably low in oxygen due to their density and fast metabolism – disrupting their adaptation to these conditions could make them more sensitive to all sorts of other therapy.
	1.4 BIOLOGIE - TECHNOS, MODÈLES
Scientists Create the First Human-Tumor-Derived Model for Studying Rectal Cancer [Memorial Sloan Kettering] When performing surgeries or biopsies on his patients, Dr. Smith removed a little bit of tumor tissue. From the samples, the researchers were able to establish 65 rectal cancer organoids from 41 patients. This is the first time that scientists have developed a model of rectal cancer that reproduces all the characteristic features of the disease in a mouse.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
E-Cigarette Smoke Causes Lung Cancer in Mice [NYU Langone Health] Dr. Tang acknowledges the study’s limitations, including that it was conducted in a relatively small number of mice susceptible to developing cancer over their lifetime (a one-year study period designed to offset age-related cancer). The study mice also did not inhale smoke like a human would, but instead, were surrounded by it through whole-body exposure.
expert reaction to study on ecig vapour and cancer in mice [Science Media Center] The study has unclear relevance for human vapers. Rodents were exposed to what are for them huge concentrations of chemicals that bear no resemblance to human exposure from vaping. Several animals in fact died during these exposures.
	4.12 BIOPSIES LIQUIDES
Predicting lung cancer’s return at surgery [Cancer Research UK] The new study, published in Nature Medicine,shows that if potential tumour cells are detected in the blood during surgery, it’s a good indicator that lung cancer will return. It’s still early days, so far only 100 patient blood samples have been analysed.
GRAIL Announces Positive Validation Data for its Multi-Cancer Early Detection Test [Grail] The results from this validation analysis demonstrate the ability of GRAIL’s technology to detect more than 20 cancer types across all stages with a single, very low false positive rate. When cancer was detected, the test also identified where the cancer was located in the body (the tissue of origin) with high accuracy.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
All For BRCA, BRCA For All? [The DNA Exchange] Population BRCA screening may prove to be cost-effective but that does not necessarily mean it would be the best use of limited health care dollars and resources. It is not exactly a zero sum game, but no matter how you slice and dice it, all health care problems cannot be covered with even the most generous allocation of resources.
	5.10 TRAITEMENTS - ESSAIS
Lilly touts Cyramza lung cancer data, but can it hang with AZ's Tagrisso? [Fierce Pharma] Lilly has already submitted the data to the FDA for a potential green light. If approved, it could mark Cyramza’s sixth indication after its recent nod in hepatocellular carcinoma with high levels of alpha-fetoprotein.
Lilly's CYRAMZA® (ramucirumab) Phase 3 Data in First-Line EGFR-Mutated Non-Small Cell Lung Cancer Published in The Lancet Oncology [Lilly] CYRAMZA, in combination with erlotinib, significantly delayed disease progression in previously untreated patients with metastatic non-small cell lung cancer whose tumors have activating EGFR mutations.
	5.2 PHARMA
U.K. launches trial of Boston Pharma's resistance-busting combo in triple-negative breast cancer [Fierce Biotech] Boston Pharmaceuticals was launched in 2015 by pharma veteran Chris Viehbacher’s Gurnet Point, which put $600 million into the startup. Since then, it has nabbed several early-stage drugs as it works toward a goal of getting at least 20 assets into clinical trials.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
FDA leaders worry agency will lose out on talent in gene therapy, cancer fields [Biopharma Dive] In fast-moving fields, the FDA has also had difficulty filling its advisory committees with relevant, non-conflicted experts.
Is FDA Too Lax With its Drug Approval Standards? Senior FDA Officials Discuss [RAPS] Gideon Blumenthal, deputy director of FDA’s Office of Oncology Excellence (OCE), added that overall survival “is the gold standard endpoint” for oncology drugs, and “that’s what we always want to attain but there are circumstances where patient populations are getting smaller and smaller, and it would be impossible to detect overall survival.”
	5.6.8 ESMO - CÔLON-RECTUM
Third-Line Treatment in Metastatic Colorectal Cancer Poised to Evolve [OBR] The story that led to the as-yet unpublished clinical study involves converging progress in understanding how macrophages mediate checkpoint inhibitor resistance and how multikinase inhibitors alter macrophage activity, particularly through effects on colony stimulating factor 1 (CSF-1) receptors.
	6.10 POLITIQUES
Top scientists accuse Boris Johnson of ‘behaving like a clown’ over research funding [The Guardian] Nurse, one of the commission’s chief scientific advisers, agrees. “I was in Brussels last week and if we crash out as Boris says, I don’t think we stand any chance of joining Horizon Europe.”
	6.11 PATIENTS
Want to Learn More About Breast Cancer? Read This Book [NY Times] “Breast cancer is emotional,” Pickert writes. And then she reveals how physicians, pharmaceutical companies and even patient advocacy groups have tapped into those emotions to prevent patients from making informed decisions about screening and treatment.
	6.5 MÉDECINES ALTERNATIVES/COMPLÉMENTAIRES
A horrifying survey of “pediatric naturopathic oncology” practice [Science-Based Medicine] “Naturopathic oncology” is a specialty made up by naturopaths in order to justify using their quackery to treat cancer patients. A new survey takes it a step further and looks at using naturopathy to treat children with cancer, including the use of homeopathy, reiki, and restrictive diets.