Targeted down regulation of TGF-beta2 in pancreatic carcinoma: A phase I/II dose escalation study to evaluate the safety and tolerability of the antisense oligonucleotide AP 12009

Schlingensiepen, Karl‐Hermann; Bischof, A.; Egger, Tamara; Hafner, M.; Herrmuth, H.; Kielmanowicz, M.; Ludwig, Stephan; Schmaus, S.; Stauder, G.

doi:10.1200/jco.2005.23.16_suppl.4253

Cited by 4 publications

(3 citation statements)

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“…Systemic and local tolerability studies in rodents, rabbits and monkeys showed a favourable toxicology profile. Based on these clinical data and the preclinical efficacy in pancreatic carcinoma, a multisite dose-escalation trial with AP 12009 in pancreatic carcinoma patients has been started to assess the maximum tolerated dose [110].…”

Section: Tgf (Transforming Growth Factor)-β2mentioning

confidence: 99%

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Antisense therapy in malignant diseases: status quo and quo vadis?

Tamm

2006

Clinical Science

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Preclinical and clinical studies indicate a role for AS ODNs (antisense oligonucleotides) as therapeutics for malignant diseases. The principle of antisense technology is the sequence-specific binding of an AS ODN to the target mRNA, resulting in a translational arrest. The specificity of hybridization makes antisense strategy attractive to selectively modulate the expression of genes involved in the pathogenesis of malignant diseases. One antisense drug has been approved for local therapy of CMV (cytomegalovirus) retinitis, and a number of AS ODNs are currently being tested in clinical trials, including AS ODN targeting Bcl-2, XIAP (X-linked inhibitor of apoptosis protein) and TGF-beta-2 (transforming growth factor beta-2). AS ODNs are well tolerated and may have therapeutic activity. In particular, an AS ODN to Bcl-2 has been tested in phase III clinical trials in chronic lymphocytic leukaemia, multiple myeloma and malignant melanoma. In this review, therapeutic concepts, clinical studies and new promising molecular targets to treat malignancies with AS ODNs are summarized.

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Section: Tgf (Transforming Growth Factor)-β2mentioning

confidence: 99%

“…Another phase I trial tested this AS ODN in pancreatic cancer [110]. AP 12009 was tested for its antitumour activity in various preclinical studies in pancreatic carcinoma.…”

Section: Tgf (Transforming Growth Factor)-β2mentioning

confidence: 99%

Antisense therapy in malignant diseases: status quo and quo vadis?

Tamm

2006

Clinical Science

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“…Its overexpression in pancreatic cancer closely correlates with advanced tumor stage. Trabedersen (AP 12009) is a phosphorothioate antisense oligonucleotide specific for TGFb-2 mRNA [101].…”

Section: Anti-tgfb-2mentioning

confidence: 99%

Novel agents for the treatment of adenocarcinoma of the pancreas

Mackenzie¹,

McCollum²

2009

Expert Review of Anticancer Therapy

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Pancreatic cancer is a particularly challenging malignancy, given its usually advanced stage at diagnosis and its rather limited treatment options. Gemcitabine has been standard therapy for advanced pancreatic cancer for well over a decade. The addition of capecitabine or erlotinib to gemcitabine has resulted in modestly improved, although still poor, overall survival. The majority of the recently completed randomized trials, however, have failed to demonstate an improvement of newer treatments over single-agent gemcitabine. Efforts currently underway center on new cytotoxic chemotherapy drugs, as well as novel targeted agents inhibiting various molecular pathways. Newly discovered proteins and cellular elements involved in tumor growth and invasion are potential therapeutic targets, and have become the focus of current trials, as well as future clinical trials. A better understanding of the biology of the disease at the basic science level, and epidemiology and risk factors from a public-health perspective, are needed. Continued research is clearly warranted with the goal of improving survival and optimizing treatment outcomes in locally advanced and metastatic pancreatic cancer.

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Nucleic Acid Therapies for Cancer Treatment

Vogl¹,

Gewirtz²

Cancer Drug Discovery and Development

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A better understanding of the biochemical pathways mediating tumor growth and progression has provided a new set of targets for therapeutic intervention. The ability to target highly specific segments of genetic material using oligonucleotide probes has been the subject of nucleic acid based therapy and is being applied to a variety of human diseases, including cancer. This chapter will discuss the various strategies utilizing nucleic acids for inhibiting gene transcription and translation with a major focus on RNAi and antisense oligodeoxynucleotides. Specific targets will be described and results of preliminary clinical trials reported. Future challenges in the clinical translation of nucleic acid treatments will also be described.

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Targeted down regulation of TGF-beta2 in pancreatic carcinoma: A phase I/II dose escalation study to evaluate the safety and tolerability of the antisense oligonucleotide AP 12009

Cited by 4 publications

References 0 publications

Antisense therapy in malignant diseases: status quo and quo vadis?

Antisense therapy in malignant diseases: status quo and quo vadis?

Novel agents for the treatment of adenocarcinoma of the pancreas

Nucleic Acid Therapies for Cancer Treatment

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