mardi 31 janvier 2012

FDA approves Erivedge (vismodegib) for basal cell carcinoma, the most common type of skin cancer

Erivedge (vismodegib) was approved yesterday by the U.S. Food and Drug Administration to treat adult patients with basal cell carcinoma, the most common type of skin cancer. The drug is intended for use in patients with locally advanced basal cell cancer who are not candidates for surgery or radiation and for patients whose cancer has spread to other parts of the body (metastatic).

Erivedge, reviewed under the agency’s priority review program, is the first FDA-approved drug for metastatic basal cell carcinoma. Erivedge was reviewed under the FDA’s priority review program that provides for an expedited six-month review of drugs that may offer major advances in treatment. The drug is being approved ahead of the March 8, 2012 prescription user fee goal date.

Basal cell carcinoma is generally a slow growing and painless form of skin cancer that starts in the top layer of the skin (epidermis). The cancer develops on areas of skin that are regularly exposed to sunlight or other ultraviolet radiation.

Erivedge is a pill taken once a day and works by inhibiting the Hedgehog pathway, a pathway that is active in most basal cell cancers and only a few normal tissues, such as hair follicles.

The most common side effects observed in patients treated with Erivedge were muscle spasms, hair loss, weight loss, nausea, diarrhea, fatigue, distorted sense of taste, decreased appetite, constipation, vomiting, and loss of taste function in the tongue.

lundi 30 janvier 2012

Mutated genes in cancer (47) – HRAS


In databases:

● Entrez ( 3265 or HRAS
● Ensembl ( ENSG00000174775
● UniProt ( P01112
● GeneCards ( HRAS
HGNC ( 5173 or HRAS

Gene locus :


Protein name:

v-Ha-ras Harvey rat sarcoma viral oncogene homolog

Protein Size:

189 amino acids; about 21 kDa


The protein encoded by this gene belongs to the Ras oncogene family, whose members are related to the transforming genes of mammalian sarcoma retroviruses. The products encoded by these genes function in signal transduction pathways. These proteins can bind GTP and GDP, and they have intrinsic GTPase activity. This protein undergoes a continuous cycle of de- and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus.

Cancer-related alterations:

Somatic HRAS mutations have been observed in tumors of salivary glands (about 15% of cases), urinary tract, upper aerodigestive tract, cervix. In most cases, mutations are substitution “missenses”. Mutation hot spots are related to amino acids 12, 13 and 61

HRAS mutations may cause Costello syndrome, a disease characterized by increased growth at the prenatal stage, growth deficiency at the postnatal stage, predisposition to tumor formation, mental retardation, skin and musculoskeletal abnormalities, distinctive facial appearance and cardiovascular abnormalities. Costello syndrome is also characterized by tumor predisposition. Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS), which is a variant of Costello syndrome.

Hurthle cell thyroid carcinoma, which accounts for approximately 3% of all thyroid cancers, is associated to HRAS genetic alterations. Although Hurthle cell thyroid carcinoma are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms.

HRAS-associated bladder cancer often presents with multiple tumors appearing at different times and at different sites in the bladder.

Oral squamous cell carcinoma (OSCC) has been associated with HRAS alterations.

References (open access):

Costello Syndrome. Gripp KW, Lin AE. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. SourceGeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.2006 Aug 29 [updated 2009 May 19].

Oncogenic RAS induces accelerated transition through G2/M and promotes defects in the G2 DNA damage and mitotic spindle checkpoints. Knauf JA, Ouyang B, Knudsen ES, Fukasawa K, Babcock G, Fagin JA. J Biol Chem. 2006 Feb 17;281(7):3800-9.

Genetic pathways and mutation profiles of human cancers: site- and exposure-specific patterns. Lea IA, Jackson MA, Li X, Bailey S, Peddada SD, Dunnick JK. Carcinogenesis. 2007 Sep;28(9):1851-8.

dimanche 29 janvier 2012

Anticancer molecules (75) – Molécules anticancéreuses (75) - AZACITIDINE


Name: azacitidine
Commercial names: Mylosar, Vidaza, Ladakamycin
Pharmacological class: cytidine analogue
Therapeutic class: antineoplastic
Action: azacitidine (5-azacytidine) is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death. As azacitidine is a ribonucleoside, it incoporates into RNA to a larger extent than into DNA. The incorporation into RNA leads to the dissembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of protein. Its incorporation into DNA leads to a covalent binding with DNA methyltransferases, which prevents DNA synthesis and subsequent cytotoxicity.

In 2011, azacitidine is approved:

            ● for use in patients with all subtypes of myelodysplastic syndromes.


Nom: azacitidine
Noms commerciaux: Mylosar, Vidaza, Ladakamycin
Classe pharmacologique: analogue de nucléoside (cytidine)
Classe thérapeutique: antinéoplasiques
Action: L’azacitidine (en fait 5-azacytidine) est un analogue chimique du nucléoside de cytosine utilisé dans l'ADN et l'ARN. L’azacitidine semble induire une activité antitumorale via deux mécanismes: 1) à faible dose, par inhibition de l'ADN méthyltransférase, provoquant l'hypométhylation de l'ADN et 2) à dose élevée, par la cytotoxicité directe sur les cellules hématopoïétiques anormales dans la moelle osseuse, via son incorporation dans l'ADN et d'ARN, ce qui entraîne la mort cellulaire L'incorporation de l’azacitidine dans l'ARN conduit au désassemblage des polyribosomes, à une altération de la méthylation et de la fonction acceptrice de l'ARN de transfert, et à l'inhibition de la production de protéines. Son incorporation dans l'ADN conduit à une liaison covalente avec l'ADN méthyltransférases, qui empêche la synthèse d'ADN et cause la cytotoxicité.

En 2011, l'azacitidine est approuvé:

            ● pour une utilisation chez les patients présentant un syndrome myélodysplasique (quel que soit le sous-type).

samedi 28 janvier 2012

Press review (January 28, 2012) – Revue de presse (28 janvier 2012)

CDC: Too few Americans getting screened for common cancers
The number of Americans being screened for colon, breast and cervical cancers still fall below national targets, federal health officials said Thursday.
By Steven Reinberg. In USA Today

Test Might Predict Risk of Lung Cancer's Return
But it's not clear yet how helpful the molecular exam will be, experts say.
By Randy Dotinga. In U.S. News & World Report

Infinity stops cancer drug (saridegib) trial, shares dive
Infinity Pharmaceuticals pulled the plug on a mid-stage trial of its experimental pancreatic cancer drug as it failed to show benefit over a placebo, wiping off over 41 percent of its market value. Data from a preliminary analysis showed that patients receiving placebo along with an anti-cancer chemotherapy drug lived longer than patients who received the Infinity drug saridegib in combination with chemotherapy.
By Anand Basu. In Reuters

Oral cancer virus affects 7 percent of Americans, study finds; also linked to cervical cancer
About 16 million Americans have oral HPV, a sexually transmitted virus more commonly linked with cervical cancer that also can cause mouth cancer, according to the first nationwide estimate.
In Washington Post

Mutated Kras Spins a Molecular Loop That Launches Pancreatic Cancer
Scientists have connected two signature characteristics of pancreatic cancer, identifying a self-perpetuating “vicious cycle” of molecular activity and a new potential target for drugs to treat one of the most lehal forms of cancer..
In Newswise.

Breast Cancer ‘Tissue Bank' Opens
Britain’s first breast cancer tissue bank has opened, supplying tumour samples to scientists around the country.
By Kyrsty Hazell. In Huffington Post

FDA approves Pfizer's Inlyta (axitinib) for kidney cancer
Pfizer's Inlyta drug for patients with advanced kidney cancer got the nod from U.S. regulators on Friday, boosting the company's plans to offset plunging Lipitor sales. The Food and Drug Administration said the drug, known generically as axitinib, was effective at treating patients who did not respond to another drug for kidney cancer
In Baltimore Sun

Long-Term Survival Benefits in Colon Cancer With Oxaliplatin
Adjuvant therapy with capecitabine plus oxaliplatin (XELOX) significantly improves overall survival, compared with bolus 5-fluorouracil/leucovorin (5-FU/LV), in patients with resected stage III colon cancer, even 6 to 7 years after the completion of treatment, according to researchers here at the 2012 Gastrointestinal Cancers Symposium.
By Barbara Boughton. In Medscape

Pink Light Burlesque: Breast Cancer Survivors Strip Down and Celebrate
Pink Light Burlesque, a free program for breast cancer survivors, helps women reclaim and celebrate their bodies — to the delight of an audience.
By Lauren Santa Cruz. In TIME

Is Genome Mapping Key to Cancer Cure?
In some medical and research circles, sequencing the human genome is a breakthrough rivaling some of most influential scientific discoveries ever made. Understanding the complexities of human DNA has lead to monumental medical innovations.
By Kristen Griffin. In

Men's hopes for robot prostate surgery unrealistic:study
Robot-assisted surgery for prostate cancer has become a hot topic in recent years, but men's expectations of the surgery - including how fast they can return to their usual physical activity -- may be too high, according to a U.S. study.
By Amy Norton. In Reuters

Drug May Slow Early Prostate Cancer: Study
Typically used for an enlarged prostate, it could prevent need for aggressive treatment.
By Denise Mann. In U.S. News & World Report

Cancer du sein : réduire la récidive par l'exercice
L'Institut Curie propose aux femmes traitées la pratique d'une activité physique qui diminue de 20 % à 50 % le risque de récidive.
Par Martine Perez. Dans Le Figaro

Cancer du sein et sexualité, un double tabou à affronter
La sexualité est rarement abordée dans les discussions patients/médecins, voire pas du tout.
Par Camille. Dans L’Express

Une nanothérapie contre le cancer du sein basée sur l'ablation thermique des tumeurs
Encore une belle avancée dans le domaine des nanotechnologies appliquées à la médecine. Une équipe du Methodist Hospital Research Institute a démontré récemment une nouvelle méthode très prometteuse pour la lutte contre le cancer.

Les hommes seraient les plus touchés par les infections orales du papillomavirus
L'infection de la bouche et de la gorge par le virus du papillome humain (VPH), un agent infectieux commun, le plus souvent transmis sexuellement, qui peut provoquer des cancers, est plus fréquente chez les hommes que chez les femmes, selon une étude publiée jeudi 26 janvier aux Etats-Unis.
Dans Le Monde

Cancer du rein métastasé : la guérison est possible !
Grâce aux nouvelles thérapies dites ciblées, des patients connaissent le bonheur de vivre de nouveau normalement
Par Anne Jeanblanc. Dans Le Point

Cancer : deux protéines clés contre la croissance des tumeurs
Plusieurs études mettent en avant le rôle de deux protéines différentes pour limiter la croissance, voire détruire certaines tumeurs. Leurs noms : AMH et Hsp90. La première ciblerait les cancers ovariens tandis que l’inhibition de la seconde aurait un champ d'action plus large. Mais il reste encore quelques problèmes à régler avant d’espérer un jour les utiliser dans des thérapies.
Par Janlou Chaput. Dans Futura-Sciences

Cancer : les facteurs environnementaux et expositions professionnelles étudiés à la loupe
L'Institut national du cancer (l’INCa) publie, pour la quatrième année consécutive, son rapport sur "La situation du cancer en France en 2011". Outre les effets néfastes de la cigarette notamment, il fait l’état des lieux des principaux facteurs de risques liés à l'environnement et aux expositions professionnelles.
Dans MaxiSciences

Le mésothéliome, 31e maladie à déclaration obligatoire
Par décret n° 2012-47 du 16 janvier 2012 (« J. O. » du 18 janvier 2012), les mésothéliomes s’ajoutent à la liste officielle des maladies à déclaration obligatoire (DO).
Par Lydia Archimède. Dans Le Quotidien du Médecin

vendredi 27 janvier 2012

FDA approves Inlyta to treat patients with a type of advanced kidney cancer

            The U.S. Food and Drug Administration today approved Inlyta (axitinib) to treat patients with advanced kidney cancer (renal cell carcinoma) who have not responded to another drug for this type of cancer.

            Renal cell carcinoma is a type of kidney cancer that starts in the lining of very small tubes in the kidney. Inlyta works by blocking certain proteins called kinases that play a role in tumor growth and cancer progression.

            Inlyta is the seventh drug that has been approved for the treatment of metastatic or advanced kidney cell cancer since 2005, after sorafenib (2005), sunitinib (2006), temsirolimus (2007), everolimus (2009), bevacizumab (2009) and pazopanib (2009).

            The most common side effects observed in greater than 20 percent of patients in the clinical study were diarrhea, high blood pressure (hypertension), fatigue, decreased appetite, nausea, loss of voice (dysphonia), hand-foot syndrome (palmar-plantar erythrodysesthesia), weight loss, vomiting, weakness (asthenia) and constipation.

Mutated genes in cancer (46) – CDKN2A


In databases :

● Entrez ( 1029 or CDKN2A
● Ensembl ( ENSG00000147889
● UniProt ( P42771
● GeneCards ( CDKN2A
● HGNC ( 1787 or CDKN2A

Gene locus:


Protein name:

Cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)

Protein Size:

156 amino acids; about 17 kDa


CDKN2A encodes P16-INK4a, a protein that interacts strongly with cyclin-dependent kinase (CDK)4 and CDK6 and inhibits their ability to interact with cyclins D. P16-INK4a is capable of inducing cell cycle arrest in G1 and G2 phases. It acts as a tumor suppressor.

Cancer-related alterations:

CDKN2A is one of the most frequently alterered genes in tumors. Somatic deletions and/or mutations of various types have been observed in tumors of the following tissues (among others): genital tract, pleura, pancreas, biliary tract, skin, upper aerodigestive tract, CNS, oesophagus, urinary tract… Somatic mutations have been found throughout the gene.
Among skin tumors, CDKN2A alterations are highly associated with cutaneous melanoma (while they are rare in uveal melanoma) and several melanoma-associated syndromes, such as:

- Cutaneous malignant melanoma type 2 (CMM2). This syndrome arises de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites. CMM2 is transmitted as an autosomal dominant trait.

- Familial atypical multiple mole melanoma carcinoma syndrome (FAMMM), in which patients have an increased risk of developing melanoma and other malignant neoplasms, for example, a pancreatic cancer (FAMMMPC). Germline CDKN2A mutations are found in approximately 40% of the FAMMM syndrome patients.

- Melanoma-astrocytoma syndrome, which is characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma.

Genetic defects in CDKN2A may also be a cause of Li-Fraumeni syndrome (LFS). LFS is a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53.

References (open access):

Main roads to melanoma. Palmieri G, Capone M, Ascierto ML, Gentilcore G, Stroncek DF, Casula M, Sini MC, Palla M, Mozzillo N, Ascierto PA. J Transl Med. 2009 Oct 14;7:86.

Familial Atypical Multiple Mole Melanoma Syndrome. Eckerle Mize D, Bishop M, Resse E, Sluzevich J. In: Riegert-Johnson DL, Boardman LA, Hefferon T, Roberts M, editors. SourceCancer Syndromes [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2009-.

The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma. Lesueur F, de Lichy M, Barrois M, Durand G, Bombled J, Avril MF, Chompret A, Boitier F, Lenoir GM; French Familial Melanoma Study Group, Bressac-de Paillerets B, Baccard M, Bachollet B, Berthet P, Bonadona V, Bonnetblanc JM, Caron O, Chevrant-Breton J, Cuny JF, Dalle S, Delaunay M, Demange L, De Quatrebarbes J, Doré JF, Frénay M, Fricker JP, Gauthier-Villars M, Gesta P, Giraud S, Gorry P, Grange F, Green A, Huiart L, Janin N, Joly P, Kérob D, Lasset C, Leroux D, Limacher JM, Longy M, Mansard S, Marrou K, Martin-Denavit T, Mateus C, Maubec E, Olivier-Faivre L, Orlandini V, Pujol P, Sassolas B, Stoppa-Lyonnet D, Thomas L, Vabres P, Venat L, Wierzbicka E, Zattara H. Br J Cancer. 2008 Jul 22;99(2):364-70.

jeudi 26 janvier 2012

Focus : Flavonoids: A versatile source of anticancer drugs.

An exponential increase in the number of studies investigating how different components of the diet interact at the molecular and cellular level to determine the fate of a cell has been witnessed. In search for anticancer drugs compelling data from laboratories, epidemiologic investigations, and human clinical trials showed that flavonoids have important effects on cancer chemoprevention and chemotherapy. In many molecular mechanisms of action for prevention against cancer, flavonoids play a major role by interacting between different types of genes and enzymes. Many mechanisms of action have been identified, including carcinogen inactivation, antiproliferation, cell cycle arrest, induction of apoptosis, inhibition of angiogenesis, antioxidation, and reversal of multidrug resistance or a combination of these mechanisms. This review focuses on the anticancer activity of flavonoids as well as their molecular mechanisms, including the treatment of mammary and prostate cancer. This review also highlights some advanced derivatives of flavonoids, which play an important role against cancer.

Source: Flavonoids: A versatile source of anticancer drugs. Chahar MK, Sharma N (, Dobhal MP, Joshi YC. Pharmacogn Rev. 2011 Jan;5(9):1-12.
Free article available at:

On note une augmentation exponentielle du nombre d'études portant sur la manière dont les différentes composantes du régime alimentaire interagissent au niveau moléculaire et cellulaire pour déterminer le sort d'une cellule. Les enquêtes épidémiologiques et les essais cliniques humains ont montré que les flavonoïdes ont des effets importants sur la chimioprévention du cancer et la chimiothérapie. Dans de nombreux mécanismes moléculaires d'action de prévention contre le cancer, les flavonoïdes jouent un rôle majeur en interagissant entre différents types de gènes et d’enzymes. De nombreux mécanismes d'action ont été identifiés, y compris l'inactivation de carcinogènes, l’antiproliferation, l’arrêt du cycle cellulaire, l'induction de l'apoptose, l'inhibition de l'angiogénèse, l’anti-oxydation, et le renversement de la multirésistance ou une combinaison de ces divers mécanismes. La présente revue se concentre sur l'activité anticancéreuse des flavonoïdes ainsi que sur leurs mécanismes moléculaires, y compris dans le traitement du cancer mammaire et de la prostate. Cette revue met également en évidence certains dérivés de flavonoïdes qui jouent un rôle important contre le cancer.

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

mercredi 25 janvier 2012

Focus: Choriocarcinoma of the breast; a case report and review of literatures.

Choriocarcinoma is an extremely rare pathology among breast malignancies. It is introduced by two distinct terms in the literatures: breast cancer with choriocarcinomatous features and metastatic choriocarcinoma to the breast. In this case report, the history, physical examination, laboratory findings, imaging studies, and pathological findings of breast choriocarcinoma in a 41-year-old woman are described and previous literatures about choriocarcinoma in the breast are reviewed.

Source: Choriocarcinoma of the breast; a case report and review of literatures. Hemati S (, Esnaashari O, Mohajeri M, Sarvizadeh M. J Res Med Sci. 2011 May;16(5):707-11.
Free article available at:

Le choriocarcinome est une pathologie extrêmement rare parmi les tumeurs malignes du sein. Il est désigné par deux termes distincts dans la littérature: cancer du sein avec des caractéristiques choriocarcinomateuses et choriocarcinome métastatique dans le sein. Dans le présent rapport de cas, l'histoire, l'examen physique, les résultats de laboratoire, les études d'imagerie, et les observations pathologiques d’un choriocarcinome du sein chez une femme de 41 ans sont décrits et la littérature existante sur le choriocarcinome dans le sein est passée en revue.

Article (en anglais) disponible à l’adresse :

Synonyms - Synonymes (January 25, 2012 – 25 janvier 2012)

Name (nom)
Synonyms (synonymes)

BBR 2778
IMC-1121b, IMC 1121B, LY3009806
MT103, MT-103, MEDI-538