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Pharma Strategy Blog
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by Sally Church in Pharma Strategy Blog
One of the interesting things about basic cancer research is that new targets emerge all the time, offering fresh opportunities…
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Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W., Fedorov, O., Morse, E., Keates, T., Hickman, T., Felletar, I.... (2010) Selective inhibition of BET bromodomains. Nature, 468(7327), 1067-1073. DOI: 10.1038/nature09504
Puissant, A., Frumm, S., Alexe, G., Bassil, C., Qi, J., Chanthery, Y., Nekritz, E., Zeid, R., Gustafson, W., Greninger, P.... (2013) Targeting MYCN in Neuroblastoma by BET Bromodomain Inhibition. Cancer Discovery, 3(3), 308-323. DOI: 10.1158/2159-8290.CD-12-0418
Lin, C., Lovén, J., Rahl, P., Paranal, R., Burge, C., Bradner, J., Lee, T., & Young, R. (2012) Transcriptional Amplification in Tumor Cells with Elevated c-Myc. Cell, 151(1), 56-67. DOI: 10.1016/j.cell.2012.08.026
Mertz, J., Conery, A., Bryant, B., Sandy, P., Balasubramanian, S., Mele, D., Bergeron, L., & Sims, R. (2011) Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proceedings of the National Academy of Sciences, 108(40), 16669-16674. DOI: 10.1073/pnas.1108190108
Schnepp, R., & Maris, J. (2013) Targeting MYCN: A Good BET for Improving Neuroblastoma Therapy?. Cancer Discovery, 3(3), 255-257. DOI: 10.1158/2159-8290.CD-13-0018
by Sally Church in Pharma Strategy Blog
After highlighting the interesting biomarker program associated with AVEO’s tivozanib in renal cell and triple negative breast cancers in the last…
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Garon, E., Finn, R., Hosmer, W., Dering, J., Ginther, C., Adhami, S., Kamranpour, N., Pitts, S., Desai, A., Elashoff, D.... (2010) Identification of Common Predictive Markers of In vitro Response to the Mek Inhibitor Selumetinib (AZD6244; ARRY-142886) in Human Breast Cancer and Non-Small Cell Lung Cancer Cell Lines. Molecular Cancer Therapeutics, 9(7), 1985-1994. DOI: 10.1158/1535-7163.MCT-10-0037
Sarli, V., & Giannis, A. (2008) Targeting the Kinesin Spindle Protein: Basic Principles and Clinical Implications. Clinical Cancer Research, 14(23), 7583-7587. DOI: 10.1158/1078-0432.CCR-08-0120
Tunquist, B., Woessner, R., & Walker, D. (2010) Mcl-1 Stability Determines Mitotic Cell Fate of Human Multiple Myeloma Tumor Cells Treated with the Kinesin Spindle Protein Inhibitor ARRY-520. Molecular Cancer Therapeutics, 9(7), 2046-2056. DOI: 10.1158/1535-7163.MCT-10-0033
by Sally Church in Pharma Strategy Blog
Today is the 1000th blog post here on PSB, a milestone I never imagined actually reaching while writing the inaugural…
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Jänne, P., Shaw, A., Pereira, J., Jeannin, G., Vansteenkiste, J., Barrios, C., Franke, F., Grinsted, L., Zazulina, V., Smith, P.... (2012) Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. The Lancet Oncology. DOI: 10.1016/S1470-2045(12)70489-8
by Sally Church in Pharma Strategy Blog
Aside from the already published Part 1 and Part 2 blog posts about AACR here on PSB, you can also find some more coverage, including summaries of other topics, on the companion Biotech Strategy Blog, such as the following: SARDs, … Continue reading →
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Sun, J., Liu, Q., Wang, J., Ahluwalia, D., Ferraro, D., Wang, Y., Duan, J., Ammons, W., Curd, J., Matteucci, M.... (2011) Selective Tumor Hypoxia Targeting by Hypoxia-Activated Prodrug TH-302 Inhibits Tumor Growth in Preclinical Models of Cancer. Clinical Cancer Research, 18(3), 758-770. DOI: 10.1158/1078-0432.CCR-11-1980
by Sally Church in Pharma Strategy Blog
One of the biggest challenges facing cancer research was aptly summarised by Levi Garraway and Pasi Jänne in this month’s Cancer Discovery journal: “All successful cancer therapies are limited by the development of drug resistance. The increase in the understanding … Continue reading →
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Garraway, L., & Janne, P. (2012) Circumventing Cancer Drug Resistance in the Era of Personalized Medicine. Cancer Discovery, 2(3), 214-226. DOI: 10.1158/2159-8290.CD-12-0012
Doebele, R., Pilling, A., Aisner, D., Kutateladze, T., Le, A., Weickhardt, A., Kondo, K., Linderman, D., Heasley, L., Franklin, W.... (2012) Mechanisms of Resistance to Crizotinib in Patients with ALK Gene Rearranged Non-Small Cell Lung Cancer. Clinical Cancer Research, 18(5), 1472-1482. DOI: 10.1158/1078-0432.CCR-11-2906
Katayama, R., Shaw, A., Khan, T., Mino-Kenudson, M., Solomon, B., Halmos, B., Jessop, N., Wain, J., Yeo, A., Benes, C.... (2012) Mechanisms of Acquired Crizotinib Resistance in ALK-Rearranged Lung Cancers. Science Translational Medicine, 4(120), 120-120. DOI: 10.1126/scitranslmed.3003316
by Sally Church in Pharma Strategy Blog
Cancer metabolism is fast becoming an area to watch out for in R&D. Last month I tweeted that I was attending a one day meeting at NY Academy of Sciences on Cancer Metabolism with keynote speakers Drs Lou Cantley and … Continue reading →
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Vander Heiden MG, Cantley LC, & Thompson CB. (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science (New York, N.Y.), 324(5930), 1029-33. PMID: 19460998
Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, Pfeiffer HK, Nissim I, Daikhin E, Yudkoff M, McMahon SB.... (2008) Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proceedings of the National Academy of Sciences of the United States of America, 105(48), 18782-7. PMID: 19033189
Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, Heffron G, Metallo CM, Muranen T, Sharfi H.... (2011) Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nature genetics, 43(9), 869-74. PMID: 21804546
Adam J, Hatipoglu E, O'Flaherty L, Ternette N, Sahgal N, Lockstone H, Baban D, Nye E, Stamp GW, Wolhuter K.... (2011) Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling. Cancer cell, 20(4), 524-37. PMID: 22014577
Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC.... (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature, 462(7274), 739-44. PMID: 19935646
Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF.... (2010) Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer cell, 18(6), 553-67. PMID: 21130701
by Sally Church in Pharma Strategy Blog
Back in 2009 at the American Association for Cancer Research (AACR) Molecular Targets meeting, a researcher (Anirban Maitra) from Boston had a most interesting poster about the use of nanotechnology to deliver nab-paclitaxel (Abraxane) to pancreatic adenocarcinomas in a more … Continue reading →
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Frese, K., Neesse, A., Cook, N., Bapiro, T., Lolkema, M., Jodrell, D., & Tuveson, D. (2012) nab-Paclitaxel Potentiates Gemcitabine Activity by Reducing Cytidine Deaminase Levels in a Mouse Model of Pancreatic Cancer. Cancer Discovery. DOI: 10.1158/2159-8290.CD-11-0242
by Sally Church in Pharma Strategy Blog
Greetings from the European Association of Urology (EAU) congress in Paris. Despite the grey drizzle typical of Europe in winter, this is actually quite an interesting meeting with lots of poster presentations. One poster that caught my eye yesterday was … Continue reading →
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Miyake H, Nelson C, Rennie PS, & Gleave ME. (2000) Testosterone-repressed prostate message-2 is an antiapoptotic gene involved in progression to androgen independence in prostate cancer. Cancer research, 60(1), 170-6. PMID: 10646870
by Sally Church in Pharma Strategy Blog
A couple of recent controversies in the field of angiogenesis have fascinated scientists and clinicians alike, namely: Does VEGF inhibition lead to more aggressive tumours? What drives metastases and invasion? What is the role of tumour hypoxia in this process? … Continue reading →
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Sennino, B., Ishiguro-Oonuma, T., Wei, Y., Naylor, R., Williamson, C., Bhagwandin, V., Tabruyn, S., You, W., Chapman, H., Christensen, J.... (2012) Suppression of Tumor Invasion and Metastasis by Concurrent Inhibition of c-Met and VEGF Signaling in Pancreatic Neuroendocrine Tumors. Cancer Discovery. DOI: 10.1158/2159-8290.CD-11-0240
by Sally Church in Pharma Strategy Blog
During my years in Pharmaland, I often sat in waiting rooms waiting to see the Principal Investigator (PI) for one of the studies we were doing. I would generally see them at the end of the clinic, preferring to arrive … Continue reading →
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Stone, R., Nick, A., McNeish, I., Balkwill, F., Han, H., Bottsford-Miller, J., Rupaimoole, R., Armaiz-Pena, G., Pecot, C., Coward, J.... (2012) Paraneoplastic Thrombocytosis in Ovarian Cancer. New England Journal of Medicine, 366(7), 610-618. DOI: 10.1056/NEJMoa1110352
Coward, J., Kulbe, H., Chakravarty, P., Leader, D., Vassileva, V., Leinster, D., Thompson, R., Schioppa, T., Nemeth, J., Vermeulen, J.... (2011) Interleukin-6 as a Therapeutic Target in Human Ovarian Cancer. Clinical Cancer Research, 17(18), 6083-6096. DOI: 10.1158/1078-0432.CCR-11-0945
by Sally Church in Pharma Strategy Blog
Every now and then my eye is caught by reports of new fusion genes being found in different cancers. Often these descriptions involve researchers across multiple laboratories due to the rarity of the target. Following a discussion on Twitter yesterday, … Continue reading →
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Tanas, M., Sboner, A., Oliveira, A., Erickson-Johnson, M., Hespelt, J., Hanwright, P., Flanagan, J., Luo, Y., Fenwick, K., Natrajan, R.... (2011) Identification of a Disease-Defining Gene Fusion in Epithelioid Hemangioendothelioma. Science Translational Medicine, 3(98), 98-98. DOI: 10.1126/scitranslmed.3002409
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
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
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
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
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
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
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
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
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
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