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Pharma Strategy Blog
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- February 10, 2012
- 04:24 PM
- 36 views
The role of the Androgen Receptor in breast cancer
by Sally Church in Pharma Strategy Blog
This week I have been in Orlando for the American Association for Cancer Research (AACR) Special Conference on prostate cancer chaired by Drs Arul Chinnaiyan (U. of Michigan) and Charles Sawyers (MSKCC). It was a superb meeting, probably one of … Continue reading →
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Hu, R., Dawood, S., Holmes, M., Collins, L., Schnitt, S., Cole, K., Marotti, J., Hankinson, S., Colditz, G., & Tamimi, R. (2011) Androgen Receptor Expression and Breast Cancer Survival in Postmenopausal Women. Clinical Cancer Research, 17(7), 1867-1874. DOI: 10.1158/1078-0432.CCR-10-2021
- February 2, 2012
- 11:39 AM
- 6 views
Is ARN-509 (Aragon) potentially better than MDV-3100 (Medivation) in advanced prostate cancer?
by Sally Church in Pharma Strategy Blog
Many readers will have noticed that the advanced prostate cancer market is rapidly becoming crowded with three new therapies (cabazitaxel, sipuleucel-T and abiraterone) already approved and several more in late stage development, including Alpharadin (radium-223) and MDV3100, both likely to … Continue reading →
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Clegg, N., Wongvipat, J., Tran, C., Ouk, S., Dilhas, A., Joseph, J., Chen, Y., Grillot, K., Bischoff, E., Cai, L.... (2012) ARN-509: a novel anti-androgen for prostate cancer treatment. Cancer Research. DOI: 10.1158/0008-5472.CAN-11-3948
Scher, H. (2005) Biology of Progressive, Castration-Resistant Prostate Cancer: Directed Therapies Targeting the Androgen-Receptor Signaling Axis. Journal of Clinical Oncology, 23(32), 8253-8261. DOI: 10.1200/JCO.2005.03.4777
- January 31, 2012
- 06:09 PM
- 104 views
Update on Medivation’s MDV3100 in advanced prostate cancer
by Sally Church in Pharma Strategy Blog
This weekend heralds the annual American Society of Clinical Oncology (ASCO) Genitourinary (GU) meeting in San Francisco, although ASCO held their press briefing today to provide an update on some of the key topics. For those of you interested in … Continue reading →
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Chen CD, Welsbie DS, Tran C, Baek SH, Chen R, Vessella R, Rosenfeld MG, & Sawyers CL. (2004) Molecular determinants of resistance to antiandrogen therapy. Nature medicine, 10(1), 33-9. PMID: 14702632
Carver, B., Chapinski, C., Wongvipat, J., Hieronymus, H., Chen, Y., Chandarlapaty, S., Arora, V., Le, C., Koutcher, J., Scher, H.... (2011) Reciprocal Feedback Regulation of PI3K and Androgen Receptor Signaling in PTEN-Deficient Prostate Cancer. Cancer Cell, 19(5), 575-586. DOI: 10.1016/j.ccr.2011.04.008
- January 31, 2012
- 08:08 AM
- 60 views
On KRAS, NF-kB activation and pancreatic cancer
by Sally Church in Pharma Strategy Blog
Pancreatic cancer as many readers know, is one of those cancers that is generally diagnosed later than most in stage IV and as a result, has a poor prognosis, often only a year or so from diagnosis. It has been … Continue reading →
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Ling, J., Kang, Y., Zhao, R., Xia, Q., Lee, D., Chang, Z., Li, J., Peng, B., Fleming, J., Wang, H.... (2012) KrasG12D-Induced IKK2/β/NF-κB Activation by IL-1α and p62 Feedforward Loops Is Required for Development of Pancreatic Ductal Adenocarcinoma. Cancer Cell, 21(1), 105-120. DOI: 10.1016/j.ccr.2011.12.006
- January 26, 2012
- 03:12 PM
- 27 views
A new opportunity for vemurafenib in BRAFV600E colon cancer
by Sally Church in Pharma Strategy Blog
There’s been quite a flurry of commercial news on the Pharma front this morning, with Amgen buying Micromet (whose leading product is blinatumumab in ALL) and Celgene announcing their acquisition of Avila Therapeutics who have a Bruton Kinase Inhibitor (BTK) … Continue reading →
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Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., Beijersbergen, R., Bardelli, A., & Bernards, R. (2012) Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature. DOI: 10.1038/nature10868
- January 24, 2012
- 12:56 PM
- 126 views
Unravelling early colorectal cancer: the links between ROS, DNA methylation and inflammatory responses
by Sally Church in Pharma Strategy Blog
During yesterday’s discussion with Dr Ray DuBois (MD Anderson Cancer Center) about inflammation and methylation, the topic of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) came up as you can see from the brief audio clip below: Steve … Continue reading →
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O'Hagan, H., Wang, W., Sen, S., DeStefano Shields, C., Lee, S., Zhang, Y., Clements, E., Cai, Y., Van Neste, L., Easwaran, H.... (2011) Oxidative Damage Targets Complexes Containing DNA Methyltransferases, SIRT1, and Polycomb Members to Promoter CpG Islands. Cancer Cell, 20(5), 606-619. DOI: 10.1016/j.ccr.2011.09.012
Federico A, Morgillo F, Tuccillo C, Ciardiello F, & Loguercio C. (2007) Chronic inflammation and oxidative stress in human carcinogenesis. International journal of cancer. Journal international du cancer, 121(11), 2381-6. PMID: 17893868
Xia, D., Wang, D., Kim, S., Katoh, H., & DuBois, R. (2012) Prostaglandin E2 promotes intestinal tumor growth via DNA methylation. Nature Medicine. DOI: 10.1038/nm.2608
- January 23, 2012
- 12:29 PM
- 117 views
New research demonstrates the link between inflammation and early development of colon cancer
by Sally Church in Pharma Strategy Blog
Recently, epigenetics has been very much to the forefront with promising new human data in lung and breast cancers. This morning I was therefore thrilled to see some exciting work just published in Nature Medicine Online First from Ray DuBois’s … Continue reading →
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Wang, D., & DuBois, R. (2009) The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene, 29(6), 781-788. DOI: 10.1038/onc.2009.421
Xia, D., Wang, D., Kim, S., Katoh, H., & DuBois, R. (2012) Prostaglandin E2 promotes intestinal tumor growth via DNA methylation. Nature Medicine. DOI: 10.1038/nm.2608
- January 16, 2012
- 11:18 AM
- 57 views
miRNA as a potential biomarker for early breast cancer
by Sally Church in Pharma Strategy Blog
One way to potentially improve long term cancer statistics is earlier detection, and in high risk patients, appropriate initiation of earlier treatment, since it is well known that the survival in stage II or III breast cancer is noticeably better … Continue reading →
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Schrauder, M., Strick, R., Schulz-Wendtland, R., Strissel, P., Kahmann, L., Loehberg, C., Lux, M., Jud, S., Hartmann, A., Hein, A.... (2012) Circulating Micro-RNAs as Potential Blood-Based Markers for Early Stage Breast Cancer Detection. PLoS ONE, 7(1). DOI: 10.1371/journal.pone.0029770
Lee, R., Feinbaum, R., & Ambros, V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75(5), 843-854. DOI: 10.1016/0092-8674(93)90529-Y
Foss KM, Sima C, Ugolini D, Neri M, Allen KE, & Weiss GJ. (2011) miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 6(3), 482-8. PMID: 21258252
Boeri M, Verri C, Conte D, Roz L, Modena P, Facchinetti F, Calabrò E, Croce CM, Pastorino U, & Sozzi G. (2011) MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proceedings of the National Academy of Sciences of the United States of America, 108(9), 3713-8. PMID: 21300873
Häusler, S., Keller, A., Chandran, P., Ziegler, K., Zipp, K., Heuer, S., Krockenberger, M., Engel, J., Hönig, A., Scheffler, M.... (2010) Whole blood-derived miRNA profiles as potential new tools for ovarian cancer screening. British Journal of Cancer, 103(5), 693-700. DOI: 10.1038/sj.bjc.6605833
- January 5, 2012
- 04:03 PM
- 43 views
Gene mutation and resistance to chemotherapy in colorectal cancer
by Sally Church in Pharma Strategy Blog
This week’s New England Journal of Medicine (NEJM) contained a fascinating article on how a specific gene mutation known as Transcription factor AP-2 epsilon, TFAP2E–DKK4, appears to be responsible for inducing at least some of the resistance to chemotherapy that … Continue reading →
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Ebert, M., Tänzer, M., Balluff, B., Burgermeister, E., Kretzschmar, A., Hughes, D., Tetzner, R., Lofton-Day, C., Rosenberg, R., Reinacher-Schick, A.... (2012) TFAP2E–DKK4 and Chemoresistance in Colorectal Cancer. New England Journal of Medicine, 366(1), 44-53. DOI: 10.1056/NEJMoa1009473
Xi, Y., Nakajima, G., Schmitz, J., Chu, E., & Ju, J. (2006) Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics, 7(1), 68. DOI: 10.1186/1471-2164-7-68
- December 10, 2011
- 02:48 PM
- 31 views
What’s hot at SABCS – Update 2 – advanced breast cancer
by Sally Church in Pharma Strategy Blog
After a number of basic research and science sessions over the last two days (see the Update 1 post on the science that intrigued me for more details), but the last two days heralded some excellent clinical sessions, in both … Continue reading →
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Baselga, J., Campone, M., Piccart, M., Burris, H., Rugo, H., Sahmoud, T., Noguchi, S., Gnant, M., Pritchard, K., Lebrun, F.... (2011) Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer. New England Journal of Medicine, 2147483647. DOI: 10.1056/NEJMoa1109653
Baselga, J., Cortés, J., Kim, S., Im, S., Hegg, R., Im, Y., Roman, L., Pedrini, J., Pienkowski, T., Knott, A.... (2011) Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer. New England Journal of Medicine, 2147483647. DOI: 10.1056/NEJMoa1113216
Gradishar, W. (2011) HER2 Therapy — An Abundance of Riches. New England Journal of Medicine, 2147483647. DOI: 10.1056/NEJMe1113641
- December 1, 2011
- 10:46 AM
- 86 views
EGFR activates mTORC2 in glioblastoma – a potential role for new therapies
by Sally Church in Pharma Strategy Blog
One of the great things about following the American Association for Cancer Research (AACR) on Twitter, is that they regularly share technical open access articles from their journals for scientists to read. Of course, many will have access through their … Continue reading →
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Tanaka, K., Babic, I., Nathanson, D., Akhavan, D., Guo, D., Gini, B., Dang, J., Zhu, S., Yang, H., De Jesus, J.... (2011) Oncogenic EGFR Signaling Activates an mTORC2-NF- B Pathway That Promotes Chemotherapy Resistance. Cancer Discovery, 1(6), 524-538. DOI: 10.1158/2159-8290.CD-11-0124
Cloughesy TF, Yoshimoto K, Nghiemphu P, Brown K, Dang J, Zhu S, Hsueh T, Chen Y, Wang W, Youngkin D.... (2008) Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS medicine, 5(1). PMID: 18215105
Huang, P., Mukasa, A., Bonavia, R., Flynn, R., Brewer, Z., Cavenee, W., Furnari, F., & White, F. (2007) Quantitative analysis of EGFRvIII cellular signaling networks reveals a combinatorial therapeutic strategy for glioblastoma. Proceedings of the National Academy of Sciences, 104(31), 12867-12872. DOI: 10.1073/pnas.0705158104
- November 28, 2011
- 11:30 AM
- 140 views
Exciting new approach to targeted therapy in prostate cancer
by Sally Church in Pharma Strategy Blog
Last week a very interesting article appeared in Cancer Discovery that reported a new target in neuroendocrine tumours (NET) of the prostate, a particularly aggressive subtype. Now, these tumours are “rare” and “uncommon” based on a spot check with a … Continue reading →
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Beltran, H., Rickman, D., Park, K., Chae, S., Sboner, A., MacDonald, T., Wang, Y., Sheikh, K., Terry, S., Tagawa, S.... (2011) Molecular Characterization of Neuroendocrine Prostate Cancer and Identification of New Drug Targets. Cancer Discovery, 1(6), 487-495. DOI: 10.1158/2159-8290.CD-11-0130
Tomlins, S. (2005) Recurrent Fusion of TMPRSS2 and ETS Transcription Factor Genes in Prostate Cancer. Science, 310(5748), 644-648. DOI: 10.1126/science.1117679
- November 22, 2011
- 12:01 PM
- 124 views
Update from AACR Molecular Targets 2011 #2 – Angiogenesis
by Sally Church in Pharma Strategy Blog
Angiogenesis inhibitors have seen a long and rather chequered history since Judah Folkman first propounded the concept that tumours grow by adding new blood vessels. Many of these inhibitors have ended up in the dog heaven scrap heap, so to … Continue reading →
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Tobler, N. (2006) Tumor and lymph node lymphangiogenesis--impact on cancer metastasis. Journal of Leukocyte Biology, 80(4), 691-696. DOI: 10.1189/jlb.1105653
- November 21, 2011
- 04:44 PM
- 169 views
Update from AACR Molecular Targets 2011 #1 – Breast Cancer
by Sally Church in Pharma Strategy Blog
Last week I had an enjoyable time at the AACR-EORTC-NCI Molecular Targets meeting but gippy wifi in San Francisco followed by my blog hosting and RSS feed going haywire meant that reviews of the meeting were delayed until now. There … Continue reading →
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Perez-Pinera, P., Garcia-Suarez, O., Menendez-Rodriguez, P., Mortimer, J., Chang, Y., Astudillo, A., & Deuel, T. (2007) The receptor protein tyrosine phosphatase (RPTP)β/ζ is expressed in different subtypes of human breast cancer. Biochemical and Biophysical Research Communications, 362(1), 5-10. DOI: 10.1016/j.bbrc.2007.06.050
Krishnan, C., Moline, S., Anders, K., & Warnke, R. (2009) Intravascular ALK-Positive Anaplastic Large-Cell Lymphoma Mimicking Inflammatory Breast Carcinoma. Journal of Clinical Oncology, 27(15), 2563-2565. DOI: 10.1200/JCO.2008.20.3984
- November 11, 2011
- 11:59 AM
- 173 views
Epigenetics – an emerging new potential treatment for lung cancer?
by Sally Church in Pharma Strategy Blog
This study demonstrated that combined epigenetic therapy with low-dose azacitidine and entinostat resulted in objective, durable responses in patients with lung cancer and defined a blood-based biomarker that correlated with clinical benefit.... Read more »
Bird, A. (2007) Perceptions of epigenetics. Nature, 447(7143), 396-398. DOI: 10.1038/nature05913
Brock, M., Hooker, C., Ota-Machida, E., Han, Y., Guo, M., Ames, S., Glöckner, S., Piantadosi, S., Gabrielson, E., Pridham, G.... (2008) DNA Methylation Markers and Early Recurrence in Stage I Lung Cancer. New England Journal of Medicine, 358(11), 1118-1128. DOI: 10.1056/NEJMoa0706550
Huang, X., Gao, L., Wang, S., Lee, C., Ordentlich, P., & Liu, B. (2009) HDAC Inhibitor SNDX-275 Induces Apoptosis in erbB2-Overexpressing Breast Cancer Cells via Down-regulation of erbB3 Expression. Cancer Research, 69(21), 8403-8411. DOI: 10.1158/0008-5472.CAN-09-2146
Juergens, R., Wrangle, J., Vendetti, F., Murphy, S., Zhao, M., Coleman, B., Sebree, R., Rodgers, K., Hooker, C., Franco, N.... (2011) Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non-Small Cell Lung Cancer. Cancer Discovery. DOI: 10.1158/2159-8290.CD-11-0214
Rodriguez-Paredes, M., & Esteller, M. (2011) A Combined Epigenetic Therapy Equals the Efficacy of Conventional Chemotherapy in Refractory Advanced Non-Small Cell Lung Cancer. Cancer Discovery. DOI: 10.1158/2159-8290.CD-11-0271
- November 10, 2011
- 08:30 PM
- 108 views
Update on pancreatic neuroendocrine tumors (NET)
by Sally Church in Pharma Strategy Blog
The idea though, of an Awareness Day for a rare disease such as NET to improve both education and awareness seems an inherently good one to me, especially as there has been some progress clinically in 2011. According to Kulke et al., (2011) NET has an incidence of around 1 per 100,000 individuals. This excellent journal review covers the key essentials of both the disease and the treatments.... Read more »
Kulke MH, Bendell J, Kvols L, Picus J, Pommier R, & Yao J. (2011) Evolving diagnostic and treatment strategies for pancreatic neuroendocrine tumors. Journal of hematology , 29. PMID: 21672194
- November 10, 2011
- 10:32 AM
- 62 views
Update on pancreatic Neuroendocrine Tumours (NET)
by Sally Church in Pharma Strategy Blog
Today on 10th November, it’s the Second Annual Worldwide NET (Neuroendocrine Tumor) Cancer Awareness Day. Granted that’s a bit of a mouthful, but it also seems poignant given so many of my news feeds this morning were still full of … Continue reading →
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Kulke MH, Bendell J, Kvols L, Picus J, Pommier R, & Yao J. (2011) Evolving diagnostic and treatment strategies for pancreatic neuroendocrine tumors. Journal of hematology , 29. PMID: 21672194
- November 9, 2011
- 11:10 AM
- 127 views
How a metabolic protein PKM2 may have a key role in tumorigenesis
by Sally Church in Pharma Strategy Blog
There was a most intriquing Letter to Nature from Lu and colleagues at MD Anderson, describing how PKM2 (pyruvate kinase muscle) may not just have an established role to play in metabolism (via the Warburg effect in glycolysis), but how it may also have important non-metabolic functions in tumour formation and growth.... Read more »
Yang, W., Xia, Y., Ji, H., Zheng, Y., Liang, J., Huang, W., Gao, X., Aldape, K., & Lu, Z. (2011) Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature. DOI: 10.1038/nature10598
- November 9, 2011
- 11:01 AM
- 154 views
Redefining subsets of triple negative breast cancer
by Sally Church in Pharma Strategy Blog
This morning's coffee browsing in Nature Genetics brought up something that piqued my interest greatly - Haiman and colleagues sent in a Letter reporting on:
"A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer."
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Haiman, C., Chen, G., Vachon, C., Canzian, F., Dunning, A., Millikan, R., Wang, X., Ademuyiwa, F., Ahmed, S., Ambrosone, C.... (2011) A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer. Nature Genetics. DOI: 10.1038/ng.985
- November 1, 2011
- 10:54 AM
- 164 views
Understanding cancer metastasis – possible new therapeutic targets
by Sally Church in Pharma Strategy Blog
. “Scientists at Dalhousie University in Nova Scotia have identified a key mechanism of metastasis that could lead to blocking tumor growth if their findings are confirmed.” AACR press release Loved this opening to an AACR press release about a … Continue reading →
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Phipps, K., Surette, A., O'Connell, P., & Waisman, D. (2011) Plasminogen Receptor S100A10 Is Essential for the Migration of Tumor-Promoting Macrophages into Tumor Sites. Cancer Research, 71(21), 6676-6683. DOI: 10.1158/0008-5472.CAN-11-1748
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