dimanche 29 avril 2012

FDA approves Afinitor for non-cancerous kidney tumors caused by rare genetic disease

            The U.S. Food and Drug Administration recently approved Afinitor (everolimus), the first drug approved specifically to treat non-cancerous kidney tumors (renal angiomyolipomas) not requiring immediate surgery in patients with tuberous sclerosis complex (TSC).

            TSC is a rare genetic disease that causes the growth of various non-cancerous tumors in the brain, kidney and other vital organs. It affects as many as 40,000 patients in the United States, with an estimated 70 to 80 percent developing kidney problems. TSC generally causes multiple tumors in both kidneys that compress normal kidney tissues as they increase in size, leading to kidney failure and bleeding.

            Afinitor blocks the uncontrolled activity of the mTOR kinase, which plays a critical role in the development and growth of the various non-cancerous tumors occurring in patients with TSC.

            The FDA granted Afinitor orphan drug designations to treat renal angiomyolipomas and a certain type of brain tumor called subependymal giant cell astrocytoma (SEGA) in patients with TSC in 2009. An orphan designation is given to a drug intended to treat a disease or condition affecting fewer than 200,000 patients in the United States and for which the drug, based on supporting data, has shown promise in the treatment of the disease.

            The drug’s application was granted priority review, a designation given to drugs that offer major advancements in treatment or provide a treatment where no adequate therapy exists. FDA completed review of this application in four months.

            The FDA has previously approved Afinitor to treat patients with advanced renal cell carcinoma that has progressed after treatment with other cancer therapies; SEGA associated with TSC in patients who require treatment but are not candidates for surgical removal of the tumor; and progressive neuroendocrine tumors located in the pancreas that cannot be removed by surgery or that have spread to other parts of the body.

samedi 28 avril 2012

Press Review (April 28, 2012) – Revue de presse (28 avril 2012)

Healthy Behaviors Extend Life After Cancer, Experts Say
Eating well, exercising and maintaining normal weight boost survival, American Cancer Society finds.
By Jenifer Goodwin. In U.S. News & World Report

Aspirin after bowel cancer diagnosis reduces chance of dying by 30 per cent
Taking aspirin after being diagnosed with bowel cancer can reduce the chance of dying from the disease by 30 per cent, new research shows today.
In Cancer Research UK (press release)

FDA approves Glaxo cancer drug Votrient‎‎
U.S. regulators gave the nod to GlaxoSmithKline Plc's Votrient for a type of sarcoma on Thursday, following a positive advisory panel vote last month.
In Reuters.

FDA rejects Amgen's application for Xgeva
U.S. health regulators rejected the application by Amgen Inc, the world's biggest biotechnology company, to expand the use of the drug Xgeva to delay the spread of tumors to the bone in patients suffering from advanced prostate cancer.
In Reuters.

Gene Critical to Development and Spread of Lung Cancer Identified‎
A single gene that promotes initial development of the most common form of lung cancer and its lethal metastases has been identified by researchers at Mayo Clinic in Florida. Their study suggests other forms of cancer may also be driven by this gene, matrix metalloproteinase-10 (MMP-10).
In Science Daily

Post-cancer fatigue “overestimated"
Despite widespread belief to the contrary, as few as 6% of women experience cancer-related persistent fatigue a year after undergoing treatment for breast cancer, a new study has found.
In ScienceAlert

Stanford Web tool helps patients weigh cancer risk
Four years ago, Raychel Kubby Adler opted to have a prophylactic double mastectomy because of a genetic mutation that gave her an 87 percent lifetime chance of developing breast cancer. Now, the mother of two daughters and a wellness coach in Davis is considering having her ovaries removed.
By Victoria Colliver. In San Francisco Chronicle

Fewer Complications, Better Outcomes With Robot-Assisted Prostate Cancer Surgery‎
Robot-assisted surgery is now both more common and far more successful than radical "open" surgery to treat prostate cancer in the United States, according to a new Henry Ford Hospital study published in the current issue of the medical journal European Urology.
In Science Daily

Cancer: Choosing Quality of Life Over Aggressive Treatment
Amy Berman was diagnosed with terminal inflammatory breast cancer 18 months ago. To preserve her quality of life, Berman decided against aggressive treatment of her disease in favor of palliative care.
By Amy Berman. In Washington Post

Anxiety increases cancer severity in mice, study shows‎
Worrywarts, fidgety folk and the naturally nervy may have a real cause for concern: accelerated cancer. In a new study led by researchers at the Stanford University School of Medicine, anxiety-prone mice developed more severe cancer then their calm counterparts.
In Science Daily

Pourquoi les hommes ont plus de cancers que les femmes‎
Les hommes sont les premières victimes des cancers. Et comme le montre une récente étude, le constat s'applique à tous les types de cancers. Seules exceptions : ceux qui touchent les organes génitaux (utérus...) et la thyroïde.
Par Didier Raoult. Dans Le Point

Cancer de la prostate L'espoir des ultrasons‎
Des résultats prometteurs ont été obtenus en Grande-Bretagne sur 41 patients présentant une petite tumeur localisée.
Sur El Watan

Des images 3D des tissus pour repérer et traiter le cancer‎
Un dépistage plus précoce du cancer serait possible grâce à une nouvelle technique d’imagerie en 3D. Dans leur publication du American Journal of Pathology, ils décrivent leur méthode de microscopie digitale.
Dans Maxi-Sciences

Cancer du sein : pas une, mais dix maladies différentes‎
Identifiées par des chercheurs de Cambridge, ces formes nécessitent chacune un traitement particulier.
Par Damien Mascret. Dans Le Figaro

Cancer de la prostate: le dépistage sanguin sans intérêt‎
Nouvel élément d’importance dans la controverse  sur les modalités pratiques du dépistage du cancer de la prostate: le dépistage régulier (par voie sanguine) ne présente pas de véritable intérêt, et ce y compris chez les hommes considérés comme étant «à haut risque» pour cette lésion maligne.
Dans Slate.fr

vendredi 27 avril 2012

Mutated genes in cancer (67) – SMAD4


In databases:

● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 4089 or SMAD4
● Ensembl (http://www.ensembl.org/index.html): ENSG00000141646
● UniProt (http://www.uniprot.org/): Q13485
● GeneCards (http://www.genecards.org/): SMAD4
● HGNC (http://www.genenames.org/): 6770 or SMAD4

Gene locus:


Protein name:

SMAD family member 4

Protein Size:

552 amino acids; about 60 kDa


SMAD4 encodes a member of the Smad family of signal transduction proteins. Smad4 acts as an intracellular mediator of TGF-β family and activin type 1 receptor, to regulate cell growth and differentiation.

Cancer-related alterations:

Somatic mutations in SMAD4 appear frequent in pancreatic, colorectal, upper aerodigestive tract, thyroid, biliary tract cancers. About one half of these mutations are substitutions. No specific mutation hot spot has been identified. Mutant Smad4 proteins, identified in human carcinomas, were found to be impaired in their ability to regulate gene transcription.

Germline alterations of SMAD4 are a cause of juvenile polyposis syndrome (JPS or JP). JPS is an autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. Defects in SMAD4 may also be observed in some patients with juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (JP/HHT), in which JP and hereditary hemorrhagic telangiectasia (HHT) coexist in a single individual. Both JIP and HHT are autosomal dominant disorders, but with distinct and non-overlapping clinical features. HHT is a vascular malformation disorder.

References (open access):

Juvenile Polyposis Syndrome. Larsen Haidle J, Howe JR. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. SourceGeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.2003 May 13 [updated 2008 Sep 09].

Smad4-mediated TGF-beta signaling in tumorigenesis. Yang G, Yang X. Int J Biol Sci. 2010 Jan 1;6(1):1-8.

SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Blackford A, Serrano OK, Wolfgang CL, Parmigiani G, Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Eshleman JR, Goggins M, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Cameron JL, Olino K, Schulick R, Winter J, Herman JM, Laheru D, Klein AP, Vogelstein B, Kinzler KW, Velculescu VE, Hruban RH. Clin Cancer Res. 2009 Jul 15;15(14):4674-9.

jeudi 26 avril 2012

Anticancer molecules (84) – Molécules anticancéreuses (84) - THALIDOMIDE


Name: thalidomide
Commercial name: Synovir, Thalomid
Pharmacological class: immunomodulator
Therapeutic class: antinéoplasiques
Action: as a cancer treatment, thalidomide may act as a VEGF inhibitor

In 2011, thalidomide is approved:

            ● in combination with dexamethasone for the treatment of newly diagnosed multiple myeloma (MM) patients.


Nom: thalidomide
Nom commercial: Synovir, Thalomid
Classe pharmacologique: immunomodulateur
Classe thérapeutique: antinéoplasiques
Action: en tant qu’anticancéreux, la thalidomide semble agir comme un inhibiteur du VEGF

En 2011, la thalidomide est approuvée:

            ● en combinaison avec la dexaméthasone pour le traitement du myélome multiple (MM) nouvellement diagnostiqué.

mercredi 25 avril 2012

Mutated genes in cancer (66) – RB1


In databases:

● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 5925 or RB1
● Ensembl (http://www.ensembl.org/index.html): ENSG00000139687
● UniProt (http://www.uniprot.org/): P06400
● GeneCards (http://www.genecards.org/): RB1
● HGNC (http://www.genenames.org/): 9884 or RB1

Gene locus:


Protein name:

Retinoblastoma 1

Protein Size:

928 amino acids; about 106 kDa

Function :

The protein encoded by RB1 was the first tumor suppressor gene identified. It is key regulator of entry into cell division. Its active, hypophosphorylated form binds transcription factor E2F1 and represses its transcription activity, leading to cell cycle arrest. RB1 recruits and targets several histone methyltransferases, leading to epigenetic transcriptional repression. RB1 also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. RB1 has many other effects on specific targets depending on the cell type.

Cancer-related alterations:

Germinal RB1 mutations are causative for hereditary predisposition to retinoblastoma (RB), which is a congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated.
The spectrum of predisposing RB1 mutations includes large deletions (about 20%), single base substitutions (about 50%) and small length mutations (about 30%); most mutations are associated with almost complete penetrance: some rare alleles show incomplete penetrance and reduced expressivity (low penetrance retinoblastoma)

Somatic RB1 mutations: in sporadic RB, both RB1 alleles are somatically mutated. Somatic RB1 mutations are found in a variety of tumors affecting eye (about 50% of cases), urinary tract and bladder, endometrium, breast, bone (osteogenic sarcoma), lung, ovary, liver, stomach…
Deletions, insertions and point mutations are observed. There are no mutational hot spots.

References (open access):

Retinoblastoma. Lohmann DR, Gallie BL. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. SourceGeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2000 Jul 18 [updated 2010 Jun 10].

A comprehensive, sensitive and economical approach for the detection of mutations in the RB1 gene in retinoblastoma. Parsam VL, Kannabiran C, Honavar S, Vemuganti GK, Ali MJ. J Genet. 2009 Dec;88(4):517-27.

Retinoblastoma and the genetic theory of cancer: an old paradigm trying to survive to the evidence. Mastrangelo D, Hadjistilianou T, De Francesco S, Loré C. J Cancer Epidemiol. 2009;2009:301973.

lundi 23 avril 2012

Focus: Lung adenocarcinoma of never smokers and smokers harbor differential regions of genetic alteration and exhibit different levels of genomic instability.

Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS. High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas from smokers (n=39) and NS (n=30) revealed both global and regional disparities in the tumor genomes of these two groups. We found that NS lung tumors had a greater proportion of their genomes altered than those of smokers. Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more frequently in NS. We validated our findings in two independently generated public datasets. Our findings provide a novel line of evidence distinguishing genetic differences between smoker and NS lung tumors, namely, that the extent of segmental genomic alterations is greater in NS tumors. Collectively, our findings provide evidence that these lung tumors are globally and genetically different, which implies they are likely driven by distinct molecular mechanisms.

Source: Lung adenocarcinoma of never smokers and smokers harbor differential regions of genetic alteration and exhibit different levels of genomic instability. Thu KL (kthu@bccrc.ca), Vucic EA, Chari R, Zhang W, Lockwood WW, English JC, Fu R, Wang P, Feng Z, Macaulay CE, Gazdar AF, Lam S, Lam WL. PLoS One. 2012;7(3):e33003.

Des données récentes suggèrent que les distinctions cliniques observés entre les tumeurs du poumon chez les fumeurs et les personnes n'ayant jamais fumé (« NS ») vont au-delà de mutations génétiques spécifiques, telles que celles touchant les gènes EGFR, EML4-ALK, et KRAS, dont certaines ont donné lieu à des thérapies ciblées. Les altérations moléculaires identifiées à ce jour ne peuvent cependant pas expliquer tous les disparités cliniques et biologiques observées dans les tumeurs du poumon des fumeurs et des « NS ». Nous avons effectué une étude comparative à l'échelle du génome visant à identifier de nouvelles aberrations génomiques qui diffèrent entre les fumeurs et les NS.  Nous avons constaté que les tumeurs du poumon provenant des NS avaient une plus grande proportion de leurs génomes modifiés que celles des fumeurs. En outre, les gains du nombre de copies sur les chromosomes 5q, 7P, et 16p sont survenus plus fréquemment chez les NS. Nous avons validé nos conclusions dans deux ensembles indépendants de données publiques.

Article (en anglais) librement accessible à l’adresse :

vendredi 20 avril 2012

Press Review (April 21, 2012) – Revue de presse (21 avril 2012)

Breast cancer classification promises better therapies
Researchers have devised 10 categories for breast cancer tumors, an important stride toward targeting treatments more precisely. The hope is to spare patients unnecessarily toxic therapies.
By Eryn Brown. In Los Angeles Times

Pricier therapy no better for early prostate cancer‎‎
A new study suggests that expensive, high-tech proton beam radiation doesn't do any more for men with prostate cancer than the most commonly-used option.
By Genevra Pittman. In Reuters.

Levon Helm, soul of The Band, in final stages of cancer‎
Levon Helm, drummer and backbone of The Band, is in the final stages of cancer, his family said Tuesday.

Swallowing exercises can help patients with head and neck cancer
Mount Sinai School of Medicine researchers have found that targeted swallowing exercises can help alleviate swallowing dysfunction – a debilitating side effect in people undergoing chemoradiation therapy (CRT) for head and neck cancer. The study, published in the April issue of Archives of Otolaryngology – Head & Neck Surgery, a JAMA Network publication, suggests that clinicians should consider giving all patients undergoing CRT an exercise regimen to improve their quality of life after treatment.
In EurekAlert (Press Alert)

Avastin No Benefit to Older Lung Cancer Patients: Study
Adding drug to chemotherapy regimen does not prolong life for those with advanced disease, experts say.
By Steven Reinberg. In U.S. News & World Report

Breast Cancer Drug Avastin Will Not Be Available On NHS, Nice Rules
A drug will not be available to treat breast cancer on the NHS after it was unclear whether it improved survival rates, a watchdog said today.
In Huffington Post UK

Kidney-Sparing Surgery Best for Early Cancer
Medicare beneficiaries with early-stage kidney cancer appear to fare better with partial nephrectomy rather than radical surgery, a large, observational study showed.
By Todd Neale. In MedPage Today

Clues to aspirin's anti-cancer effects revealed
One of the world's oldest medicines may hold the secret to a very contemporary problem: preventing cancer. Exactly why salicylate shows such potential as an anti-cancer treatment remains unclear, but a new study in mice offers clues.
By Lisa Raffensperger. In New Scientist

Routine CT Screenings for Lung Cancer Would Detect Cancer Earlier and Save Lives
Men and women in the United States undergo regular screenings for certain cancers such as prostate cancer, breast cancer and colon cancer as part of routine medical checkups after a certain age. But patients typically don’t get screened for lung cancer, the most lethal cancer in the U.S.
In AboutMesothelioma.com

Good vibrations in fight against cancer
Magnetic nanochain detonates chemo barrage inside tumors.
In EurekAlert (Press Alert)

Cancer de la prostate : les ultrasons efficaces avec très peu d'effets secondaires
Pour la première fois, la thérapie par ultrasons focalisés de haute intensité a été utilisée dans un test clinique, chez des patients atteints d’un cancer de la prostate. Résultats : 95 % d’entre eux n’avaient plus de cancer un an après traitement, et seuls 10 % souffraient d’effets secondaires indésirables, contre 50 % en temps normal. Des résultats préliminaires très prometteurs !
Par Janlou Chaput. Dans Futura-Sciences

Cancer du poumon: les malades trop peu informés sur l'euthanasie et les soins palliatifs
La moitié seulement des personnes atteintes d'un cancer du poumon reçoivent de leur médecin les informations qu'ils demandent sur les soins palliatifs et l'euthanasie, ressort-il d'une enquête menée par la VUB et l'Université de Gand auprès de 67 patients atteints d'un cancer du poumon à un stade avancé.
Sur RTL.be

Une goutte de sang pour dépister le cancer du sein‎
Les travaux d’une équipe de chercheurs de l’Université McGill ont mené à la mise au point d’une technologie capable de mesurer les biomarqueurs protéiques liés au cancer du sein, une percée ayant fait l’objet d’un article dans le numéro d’avril de la revue scientifique Molecular& Cellular Proteomics. Cette nouvelle s’avère très encourageante : un dépistage précoce faisant augmenter les chances de réussite du traitement et la survie à long terme. Il faut savoir qu’une femme sur huit obtiendra un diagnostic de cancer du sein au cours de sa vie.
Agence Science-Presse

Patients en chimiothérapie : comment leur redonner goût à la cuisine ?‎
Subir un traitement par chimiothérapie ou radiothérapie est devenu très courant en cas de cancer. Hélas, les effets secondaires sont nombreux. L'altération de l'équilibre alimentaire en fait partie. Philippe Pouillart, enseignant-chercheur, a créé des ateliers culinaires destinés aux patients, à leurs proches et au corps médical afin qu'ils se réapproprient la cuisine.
Par Philippe Pouillart. Dans Le Nouvel Observateur

Lutte contre le cancer L'optimisation des soins par l'imagerie‎
Les nouvelles technologies de l’imagerie, une révolution pour sauver des vies.
Par Djamila Kourta. Dans El Watan

Cancer du sein: découverte d'un nouveau type de mutation
Ces chercheurs de la Mayo Clinic ont découvert une nouvelle classe de mutation moléculaire pour diverses formes de cancer du sein, une découverte qui pourrait expliquer le développement et la croissance de différents types de tumeurs mammaires. Ces formes mutées de l'ARN, dites transcrits de fusion, pourraient également fournir de nouveaux biomarqueurs de ces tumeurs et permettre de nouvelles stratégies thérapeutiques personnalisées. Les conclusions de cette étude, la première à avoir opéré une recherche systématique des transcriptions de fusion liées aux différents types de tumeurs mammaires, viennent d’être publiées dans la revue Cancer Research.
Dans Santé Log