Press Review (September 1, 2012) – Revue de presse (1 septembre 2012)

Breast Cancer Drug Might Help Men on Prostate Cancer Therapy

Study found tamoxifen cut some side effects that could discourage men from seeking treatment.

In U.S. News & World Report

http://health.usnews.com/health-news/news/articles/2012/08/28/breast-cancer-drug-might-help-men-on-prostate-cancer-therapy

Breast Cancer Drug May Harm the Heart More Than Thought‎‎

Analysis finds increased risk of cardiac problems with Herceptin in real-world setting.

By Kathleen Doheny. In U.S. News & World Report

http://health.usnews.com/health-news/news/articles/2012/08/30/breast-cancer-drug-may-harm-the-heart-more-than-thought

New prostate cancer study clouds PSA debate

A new study suggests men with advanced prostate cancer may live longer in the "PSA era" than they did before the screening test began to gain a foothold in the early 1990s.

By Frederik Joelving. In Reuters

http://www.reuters.com/article/2012/08/24/us-new-prostate-cancer-idUSBRE87N10S20120824

What Do Cancer Patients Think About Exercise?‎‎ ‎‎

Exercise is encouraged for cancer patients -- even if they are going through treatments. But a small new study from the Mayo Clinic suggests that some cancer patients still aren't prioritizing physical fitness, and their oncologists aren't talking to them about it.

In Huffington Post

http://www.huffingtonpost.com/2012/08/29/cancer-exercise-oncologists-recommendations_n_1837219.html

Exelixis says FDA drops panel talks on thyroid cancer drug‎

Exelixis Inc said U.S. regulators have dropped an advisory panel discussion on the marketing application for its experimental drug to treat a rare form of thyroid cancer, sending its shares up 6 percent after market.

In Reuters

http://www.reuters.com/article/2012/08/29/us-exelixis-fda-idUSBRE87S1E920120829

Could a cancer drug potentially prevent learning disabilities in some kids?‎

A drug originally developed to stop cancerous tumors may hold the potential to prevent abnormal brain cell growth and learning disabilities in some children, if they can be diagnosed early enough, a new animal study suggests.

In Medical Xpress

http://medicalxpress.com/news/2012-08-cancer-drug-potentially-disabilities-kids.html

Cancer gene family member functions key to cell adhesion and migration‎

The WTX gene is mutated in approximately 30 percent of Wilms tumors, a pediatric kidney cancer. Like many genes, WTX is part of a family. In this case, WTX has two related siblings, FAM123A and FAM123C. While cancer researchers are learning more of WTX and how its loss contributes to cancer formation, virtually nothing is known of FAM123C or FAM123A, the latter of which is a highly abundant protein within neurons, cells that receive and send messages from the body to the brain and back to the body

In Medical Xpress

http://medicalxpress.com/news/2012-08-cancer-gene-family-member-functions.html

Cancer : et si on le traitait à l’aide du VIH ?‎

Comment combattre le cancer, l’un des pires fléaux de l’humanité ? Des scientifiques suggèrent d’utiliser un autre de nos plus féroces ennemis : le VIH. Ou plus précisément l'une des protéines qui lui permet de se multiplier autant...

Dans Futura-Sciences

http://www.futura-sciences.com/fr/news/t/medecine/d/cancer-et-si-on-le-traitait-a-laaide-du-vih_40817/

Cancer : une molécule découverte‎‎‎‎ ‎‎

Une molécule susceptible d'agir contre les métastases, par le biais d'un nouveau mécanisme, vient d'être identifiée par des chercheurs, mais il faudra encore plusieurs années avant d'espérer passer aux premiers tests cliniques, précisent-ils.

Dans Le Figaro

http://www.lefigaro.fr/flash-actu/2012/08/28/97001-20120828FILWWW00597-cancer-une-molecule-decouverte.php

La prévention au coeur du Congrès mondial sur le cancer, à Montréal

Des spécialistes en provenance de plus de 120 pays participent au 22e Congrès mondial sur le cancer, qui s'est ouvert au Palais des congrès de Montréal lundi.

Radio-Canada.ca

http://www.radio-canada.ca/nouvelles/science/2012/08/27/001-congres-mondial-cancer-montreal-2012.shtml

Cancer : une nouvelle molécule porteuse d'espoir‎‎‎‎‎ ‎‎

Des travaux de plus de dix années ont permis de mettre à jour la molécule "Liminib" qui bloquerait la formation des métastases. Cette découverte donne de l'espoir aux patients cancéreux et pourrait, dans un premier temps, servir de traitement alternatif à la chimiothérapie d'ici quelques années.

Dans Maxisciences

http://www.maxisciences.com/cancer/cancer-une-nouvelle-molecule-porteuse-d-039-espoir_art26326.html

Synonyms - Synonymes (August 2012 – août 2012)

Name (nom)	Synonyms (synonymes)
Ibrutinib	PCI-32765
Lintuzumab	Actinium-225-HuM195, HuM195-Ac-225
Doxorubicin	DOX-LTSL, ThermoDox
Ganitumab	AMG 479, AMG479
Pracinostat	SB939
Dabrafenib	GSK2118436, GSK436
Etirinotecan pegol	NKTR-102
Trametinib	GSK1120212
Palifosfamide	isophosphoramide mustard ZIO-201, ZIO-201-T
Ponatinib	AP24534
Telotristat etiprate	LX1032, LX1606

Focus : Cancer treatment and survivorship statistics, 2012.

Although there has been considerable progress in reducing cancer incidence in the United States, the number of cancer survivors continues to increase due to the aging and growth of the population and improvements in survival rates. As a result, it is increasingly important to understand the unique medical and psychosocial needs of survivors and be aware of resources that can assist patients, caregivers, and health care providers in navigating the various phases of cancer survivorship. To highlight the challenges and opportunities to serve these survivors, the American Cancer Society and the National Cancer Institute estimated the prevalence of cancer survivors on January 1, 2012 and January 1, 2022, by cancer site. Data from Surveillance, Epidemiology, and End Results (SEER) registries were used to describe median age and stage at diagnosis and survival; data from the National Cancer Data Base and the SEER-Medicare Database were used to describe patterns of cancer treatment. An estimated 13.7 million Americans with a history of cancer were alive on January 1, 2012, and by January 1, 2022, that number will increase to nearly 18 million. The 3 most prevalent cancers among males are prostate (43%), colorectal (9%), and melanoma of the skin (7%), and those among females are breast (41%), uterine corpus (8%), and colorectal (8%). This article summarizes common cancer treatments, survival rates, and posttreatment concerns and introduces the new National Cancer Survivorship Resource Center, which has engaged more than 100 volunteer survivorship experts nationwide to develop tools for cancer survivors, caregivers, health care professionals, advocates, and policy makers.

Source: Cancer treatment and survivorship statistics, 2012. Siegel R (rebecca.siegel@cancer.org), Desantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, Lin C, Leach C, Cannady RS, Cho H, Scoppa S, Hachey M, Kirch R, Jemal A, Ward E. CA Cancer J Clin. 2012 Jul;62(4):220-41.

Free paper available at:

http://onlinelibrary.wiley.com/doi/10.3322/caac.21149/pdf

Mutated genes in cancer (79) – CDH1

CDH1

In databases :

Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 999 or CDH1

Ensembl (http://www.ensembl.org/index.html): ENSG00000039068

UniProt (http://www.uniprot.org/): P12830

OMIM (http://www.ncbi.nlm.nih.gov/omim): 192090

GeneCards (http://www.genecards.org/): CDH1

HGNC (http://www.genenames.org/): 1748 or CDH1

Gene locus:

16q22.1

Protein name:

Cadherin 1, type 1, E-cadherin (epithelial)

Protein Size:

882 amino acids; about 97 kDa

Function:

One of the most important and ubiquitous types of adhesive interactions required for the maintenance of solid tissues is that mediated by the classic cadherin adhesion molecules. Cadherins are transmembrane Ca2+- dependent homophilic adhesion receptors that are well known to play important roles in cell recognition and cell sorting during development. However, they continue to be expressed at high levels in virtually all solid tissues. There are many members of the classic cadherin family (which is a subset of the larger cadherin superfamily), but E-cadherin in epithelial tissues has been the most studied in the context of stable adhesions. Continued expression and functional activity of E-cadherin are required for cells to remain tightly associated in the epithelium, and in its absence the many other cell adhesion and cell junction proteins expressed in epithelial cells (see below) are not capable of supporting intercellular adhesion. In its capacity to maintain the overall state of adhesion between epithelial cells, E-cadherin is thought to act as an important suppressor of epithelial tumor cell invasiveness and metastasis.

Cancer-related alterations:

Mutations in this gene are correlated with gastric, breast, biliary tract, colorectal, thyroid and ovarian cancer.

Defects in CDH1 are a cause of hereditary familial diffuse gastric cancer (HDGC). Dozens of CDH1 germline mutations have been described in HDGC families. Most are inactivating (frameshift, nonsense, and splice-site), the remainders are “missense”. The mutations are distributed equally throughout the gene.

Somatic mutations in CDH1 were found in about 56% of lobular breast tumors, generally (>90%) in combination with loss of the wild-type allele, while no mutations were found in ductal primary breast carcinomas. Most of these somatic mutations result in premature stop codons as a consequence of insertions, deletions and nonsense mutations leading to the loss of the CDH1 cell-cell adhesion functionality. Other cancer-confined E-cadherin mutations also result in crippled proteins. The distinctive invasive growth pattern, which is typical for lobular breast cancers, is fully compatible with this functional inactivation.

Frequent somatic mutations (50%) in CDH have been identified in sporadic diffuse gastric cancer (DGC). Most mutations are “missense” (exons 8, 9) or exon skipping. In most cases, CDH1 mutations are found in combination with loss of the wild-type allele.

References (open access):

Pathology of hereditary breast cancer. van der Groep P, van der Wall E, van Diest PJ. Cell Oncol (Dordr). 2011 Apr;34(2):71-88.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063560/pdf/13402_2011_Article_10.pdf

Hereditary diffuse gastric cancer: prophylactic surgical oncology implications. Lynch HT, Silva E, Wirtzfeld D, Hebbard P, Lynch J, Huntsman DG. Surg Clin North Am. 2008 Aug;88(4):759-78, vi-vii.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561947/pdf/nihms67433.pdf

Germline mutations in CDH1 are infrequent in women with early-onset or familial lobular breast cancers. Schrader KA, Masciari S, Boyd N, Salamanca C, Senz J, Saunders DN, Yorida E, Maines-Bandiera S, Kaurah P, Tung N, Robson ME, Ryan PD, Olopade OI, Domchek SM, Ford J, Isaacs C, Brown P, Balmana J, Razzak AR, Miron P, Coffey K, Terry MB, John EM, Andrulis IL, Knight JA, O'Malley FP, Daly M, Bender P; kConFab, Moore R, Southey MC, Hopper JL, Garber JE, Huntsman DG. J Med Genet. 2011 Jan;48(1):64-8.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003879/pdf/jmedgenet79814.pdf

E-cadherin polymorphisms and breast cancer susceptibility: a report from the Shanghai Breast Cancer Study. Beeghly-Fadiel A, Lu W, Gao YT, Long J, Deming SL, Cai Q, Zheng Y, Shu XO, Zheng W. Breast Cancer Res Treat. 2010 Jun;121(2):445-52.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2874636/pdf/nihms172056.pdf

Focus: Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress

            The pace of exome and genome sequencing is accelerating, with the identification of many new disease-causing mutations in research settings, and it is likely that whole exome or genome sequencing could have a major impact in the clinical arena in the relatively near future. However, the human genomics community is currently facing several challenges, including phenotyping, sample collection, sequencing strategies, bioinformatics analysis, biological validation of variant function, clinical interpretation and validity of variant data, and delivery of genomic information to various constituents. Here we review these challenges and summarize the bottlenecks for the clinical application of exome and genome sequencing, and we discuss ways for moving the field forward. In particular, we urge the need for clinical-grade sample collection, high-quality sequencing data acquisition, digitalized phenotyping, rigorous generation of variant calls, and comprehensive functional annotation of variants. Additionally, we suggest that a 'networking of science' model that encourages much more collaboration and online sharing of medical history, genomic data and biological knowledge, including among research participants and consumers/patients, will help establish causation and penetrance for disease causal variants and genes. As we enter this new era of genomic medicine, we envision that consumer-driven and consumer-oriented efforts will take center stage, thus allowing insights from the human genome project to translate directly back into individualized medicine.

Source: Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress. Lyon GJ, Wang K (kaichop@gmail.com). Genome Med. 2012 Jul 26;4(7):58.

Free paper available at :

http://genomemedicine.com/content/pdf/gm359.pdf

Focus: Pathogen-driven gastrointestinal cancers: Time for a change in treatment paradigm?

            The regulation of cancerous tumor development is converged upon by multiple pathways and factors. Besides environmental factors, gastrointestinal (GI) tract cancer can be caused by chronic inflammation, which is generally induced by bacteria, viruses, and parasites. The role of these inducers in cancer development, cell differentiation and transformation, cell cycle deregulation, and in the expression of tumor-associated genes cannot be ignored. Although Helicobacter pylori activates many oncogenic pathways, particularly those in gastric and colorectal cancers, the role of viruses in tumor development is also significant. Viruses possess significant oncogenic potential to interfere with normal cell cycle control and genome stability, stimulating the growth of deregulated cells. An increasing amount of recent data also implies the association of GI cancers with bacterial colonization and viruses. This review focuses on host-cell interactions that facilitate primary mechanisms of tumorigenesis and provides new insights into novel GI cancer treatments.

Source: Pathogen-driven gastrointestinal cancers: Time for a change in treatment paradigm? Alibek K, Aituov B, Duisembekova A, Bulenova A (abulenova@nu.edu.kz). Infect Agent Cancer. 2012 Aug 8;7(1):18.

Free paper avalable at :

http://www.infectagentscancer.com/content/pdf/1750-9378-7-18.pdf

Press Review (August 25, 2012) – Revue de presse (25 août 2012)

PSA Testing Linked to Improved Prostate Cancer Survival

Analysis of research before and after screening was introduced shows benefits.

In U.S. News & World Report

http://health.usnews.com/health-news/news/articles/2012/08/23/psa-testing-linked-to-improved-prostate-cancer-survival

Radiotherapy results in higher diabetes risk for some childhood cancer survivors‎‎

The study – which analysed more than 2500 patient questionnaires and medical records from French and British people who had cancer in childhood but survived for at least 20 years after undergoing treatment – is the first to link diabetes and radiation.

In Medical Xpress

http://medicalxpress.com/news/2012-08-radiotherapy-results-higher-diabetes-childhood.html

Genome Sequencing Clears Up a Cancer Medical Mystery

Most experimental cancer drugs never make it to market because they don't help enough people in early clinical trials. But even in "failed" drug trials, researchers may find that a few patients see their tumors shrink dramatically. Since it’s not clear why some respond but most don’t, researchers typically shake their heads and move on.

By Jocelyn Kaiser. In ScienceMag

http://news.sciencemag.org/sciencenow/2012/08/genome-sequencing-clears-up-a-ca.html?ref=hp

Cancer survival in Germany after the fall of the Iron Curtain‎‎ ‎‎

Data from the 1970s and 1980s show that people affected by cancer survived significantly longer in West Germany than cancer patients behind the Iron Curtain

In Medical Xpress

http://medicalxpress.com/news/2012-08-cancer-survival-germany-fall-iron.html

Targeting inflammation to prevent, treat cancers‎

Researchers at the Georgia Health Sciences University Cancer Center have identified a gene that disrupts the inflammatory process implicated in liver cancer.

In Science Codex

http://www.sciencecodex.com/targeting_inflammation_to_prevent_treat_cancers-97137

Field guide to the Epstein-Barr virus charts viral paths toward cancer‎

Researchers from The Wistar Institute and Memorial Sloan-Kettering Cancer Center (MSKCC) have teamed to publish the first annotated atlas of the Epstein-Barr virus genome, creating the most comprehensive study of how the viral genome interacts with its human host during a latent infection.

In Science Codex

http://www.sciencecodex.com/field_guide_to_the_epsteinbarr_virus_charts_viral_paths_toward_cancer-97183

Cause of global throat cancer epidemic a mystery‎

The "astounding" increase in cases of esophageal cancer around the world seems to have begun in the UK in the 1950s, but a recent comprehensive analysis of historical data has brought scientists no closer to identifying the cause.

By Will Parker. In Science A Gogo

http://www.scienceagogo.com/news/20120722192419data_trunc_sys.shtml

Cancer: une radiothérapie durant l’enfance accroît le risque de diabète‎

C’est la première étude de la relation entre la dose de radiation reçue au niveau du pancréas et le risque ultérieur de diabète.

Dans SantéLog

http://www.santelog.com/news/diabete/cancer-du-pancreas-une-radiotherapie-a-l-enfance-multiplie-par-3-le-risque-de-diabete_8894_lirelasuite.htm

Cancer de la prostate: attention à la viande revenue à la poêle‎‎

Une étude américaine montre que les hommes qui consomment plus d'une portion et demi de viande rouge saisie à la poêle par semaine accroissent leur risque de développer un cancer de la prostate de 30%.

Dans LaPresse.ca

http://www.lapresse.ca/vivre/sante/hommes/201208/20/01-4566606-cancer-de-la-prostate-attention-a-la-viande-revenue-a-la-poele.php

Cancer de la thyroïde: l'héritage d'Hiroshima‎‎‎‎ ‎‎

Les Japonais ayant survécu aux explosions des bombes atomiques à Hiroshima et à Nagasaki ont été exposés à des risques élevés de cancer de la thyroïde pendant plus de cinquante ans après leur irradiation.

Par Cyrille Vanlerberghe. Dans Le Figaro

http://sante.lefigaro.fr/actualite/2012/08/20/18815-cancer-thyroide-tres-long-heritage-dhiroshima

Plus de risque d'un deuxième cancer chez les personnes en surpoids‎‎‎‎‎ ‎‎

Des chercheurs français ont montré que l'obésité et le surpoids pouvaient représenter un facteur de risque de second cancer, notamment après un premier cancer du sein.

Dans Canoë

http://fr.canoe.ca/artdevivre/bienetre/article1/2012/08/13/20097146-relaxnews.html

Focus: The glucose-deprivation network counteracts lapatinib-induced toxicity in resistant ErbB2-positive breast cancer cells

Dynamic interactions between intracellular networks regulate cellular homeostasis and responses to perturbations. Targeted therapy is aimed at perturbing oncogene addiction pathways in cancer, however, development of acquired resistance to these drugs is a significant clinical problem. A network-based computational analysis of global gene expression data from matched sensitive and acquired drug-resistant cells to lapatinib, an EGFR/ErbB2 inhibitor, revealed an increased expression of the glucose deprivation response network, including glucagon signaling, glucose uptake, gluconeogenesis and unfolded protein response in the resistant cells. Importantly, the glucose deprivation response markers correlated significantly with high clinical relapse rates in ErbB2-positive breast cancer patients. Further, forcing drug-sensitive cells into glucose deprivation rendered them more resistant to lapatinib. Using a chemical genomics bioinformatics mining of the CMAP database, we identified drugs that specifically target the glucose deprivation response networks to overcome the resistant phenotype and reduced survival of resistant cells. This study implicates the chronic activation of cellular compensatory networks in response to targeted therapy and suggests novel combinations targeting signaling and metabolic networks in tumors with acquired resistance.

Source: The glucose-deprivation network counteracts lapatinib-induced toxicity in resistant ErbB2-positive breast cancer cells. Komurov K, Tseng JT, Muller M, Seviour EG, Moss TJ, Yang L, Nagrath D, Ram PT. Mol Syst Biol. 2012 Jul 31;8:596.

Free paper available at:

http://www.nature.com/msb/journal/v8/n1/pdf/msb201225.pdf

Mutated genes in cancer (78) – BRCA2

BRCA2 (FANCD1)

In databases :

Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 675 or BRCA2

Ensembl (http://www.ensembl.org/index.html): ENSG00000139618

UniProt (http://www.uniprot.org/): P51587

OMIM (http://www.ncbi.nlm.nih.gov/omim): 600185

GeneCards (http://www.genecards.org/): BRCA2

HGNC (http://www.genenames.org/): 1101 or BRCA2

Gene locus:

13q12-q13

Protein name:

Breast cancer 2, early onset

Protein Size:

3418 amino acids; about 384 kDa

Function:

BRCA2 is implicated in maintenance of genomic integrity and in the cellular response to DNA damage. The BRCA2 protein interacts with the RAD51 recombinase to regulate homologous recombination (HR). CHEK1 and CHEK2 both phosphorylate the RAD51/BRCA2 complex and regulate the functional association of this complex in response to DNA damage.

BRCA2 is also implicated in cell cycle checkpoints. Following exposure to X-rays or UV light, cells expressing truncated BRCA2 protein exhibit arrest in the G1 and G2/M phases. BRCA2 protein plays a role in mitotic spindle assembly checkpoints through modulation of the level of spindle assembly checkpoint proteins including Aurora A and Aurora B.

BRCA2 may also stimulate transcription. This function of BRCA2 is regulated by the binding of the EMSY protein to the region of BRCA2 responsible for transcriptional activation. An excess of EMSY results in silencing of BRCA2-driven transcriptional activation.

Cancer-related alterations:

Defects in BRCA2 are a cause of susceptibility to breast-ovarian cancer familial type 2 (BROVCA2), a condition associated with familial predisposition to cancer of the breast and ovaries (for BROVCA1, see BRCA1; for BROVCA3, see RAD51C). Mutations at more than one locus can be involved in different families or even in the same case. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate, stomach, pharynx, gallbladder, bile duct, colon and pancreas. Cumulative risk of breast cancer in BRCA2 mutation carriers was estimated to 45% by the age of 70 years while ovarian cancer risk in carriers was estimated to 11%.

Somatic mutations in BRCA2 (substitutions, insertions, deletions) are infrequent in sporadic breast cancer. Methylation of the BRCA2 promoter has not been detected in normal tissues nor in breast and ovarian cancers. Loss of heterozygosity at the BRCA2 locus has been frequently found in sporadic breast and ovarian tumors.

Biallelic mutations of the BRCA2 gene are the cause of Fanconi anemia complementation group D type 1 (FANCD1) (see Fanconi-associated genes). Fanconi anemia (FA) is an autosomal recessive disorder affecting all bone marrow elements and associated with cardiac, renal and limb malformations as well as dermal pigmentary changes. The FANCD1 (and FANCN, see PALB2) subgroups are clinically different from other FA subgroups as these subgroups are associated with increased predisposition to solid childhood malignancies such as medulloblastoma and Wilms tumor.

At the cellular level, FA is a chromosomal fragility syndrome. FA cells are hypersensitive to DNA interstrand crosslinking agents such as mitomycin C, diepoxybutane and cisplatin. In addition to hypersensitivity to these agents, FA cells show an increased number of spontaneous breaks.

Note: information regarding breast cancer and BRCA2 mutations and polymorphisms are available in a central repository formed by the National Human Genome Research; National Institute of Health. This repository, named Breast Cancer Information Core (BIC) - NHGRI, is available at the following address: http://research.nhgri.nih.gov/bic/

Specific therapy:

Oral poly(ADP-ribose) polymerase (PARP) inhibitor olaparib shows activity in patients with advanced breast cancer or recurrent ovarian cancer and BRCA1 or BRCA2 mutations

References (open access):

Susceptibility pathways in Fanconi's anemia and breast cancer. D'Andrea AD. N Engl J Med. 2010 May 20;362(20):1909-19.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069698/pdf/nihms-215099.pdf

Pathology of hereditary breast cancer. Da Silva L, Lakhani SR. Mod Pathol. 2010 May;23 Suppl 2:S46-51.

http://www.nature.com/modpathol/journal/v23/n2s/pdf/modpathol201037a.pdf

PARP inhibitors: its role in treatment of cancer. Chen A. Chin J Cancer. 2011 Jul;30(7):463-71.

http://www.cjcsysu.cn/ENpdf/2011/7/463.pdf

JAMA patient page. BRCA genes and breast cancer. Pluta RM, Golub RM. JAMA. 2011 Jun 1;305(21):2244.

http://jama.ama-assn.org/content/305/21/2244.full.pdf+html

Focus : Advances in using PARP inhibitors to treat cancer

The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents.

Source: Advances in using PARP inhibitors to treat cancer. Kummar S, Chen A, Parchment RE, Kinders RJ, Ji J, Tomaszewski JE, Doroshow JH. BMC Med. 2012 Mar 9;10:25.

Free paper available at:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312820/pdf/1741-7015-10-25.pdf

Focus : Germline copy number variations and cancer predisposition

We present an overview of the role of germline copy number variations (CNVs) in cancer predisposition. CNVs represent a significant source of genetic diversity, although the mechanisms by which they influence cancer susceptibility still remain largely unknown. Approximately 100 highly penetrant germline mutant genes are now known to cause cancer predisposition inherited in a Mendelian fashion; in this review, we show that nearly half of these genes have also been observed as rare CNVs associated with cancer. However, these highly penetrant alleles seem to account for less than 5% of all familial cancers. We surmise that most of the genetic risk of cancer in the general population must largely involve genes of low or moderate penetrance. In the last 5 years, studies have demonstrated that although common low penetrant CNVs are modest contributors to cancer individually, their combined impact on cancer predisposition must be taken into account in estimating cancer risk.

Source: Germline copy number variations and cancer predisposition. Krepischi AC, Pearson PL, Rosenberg C (n carla.rosenberg@uol.com.br). Future Oncol. 2012 Apr;8(4):441-50.

Free paper available at:

http://www.futuremedicine.com/doi/pdf/10.2217/fon.12.34