A phase I study of AGRO100 in advanced cancer

Laber, Damian A.; Choudry, M. A.; Taft, B.; Bhupalam, L.; Sharma, Vivek R.; Hendler, F. J.; Barnhart, Kerry M.

doi:10.1200/jco.2004.22.14_suppl.3112

Cited by 7 publications

(5 citation statements)

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“…Indeed, aptameric compound AS1411, a G-rich oligonucleotide which binds to NCL with high affinity, counteracts NCL’s RNA binding activity and induces apoptosis in various cancer cells [171,172]. The therapeutic potential of AS1411 was already presented in a phase I trial for patients with different kinds of advanced cancer [173,174] and phase II trials for patients with advanced renal cell carcinoma and acute myeloid leukemia (AML) [175,176].…”

Section: Impaired Ribosome Biogenesismentioning

confidence: 99%

Impaired ribosome biogenesis: mechanisms and relevance to cancer and aging

Turi

Lacey

Mistrík

et al. 2019

Aging

165

132

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The biosynthesis of ribosomes is a complex process that requires the coordinated action of many factors and a huge energy investment from the cell. Ribosomes are essential for protein production, and thus for cellular survival, growth and proliferation. Ribosome biogenesis is initiated in the nucleolus and includes: the synthesis and processing of ribosomal RNAs, assembly of ribosomal proteins, transport to the cytoplasm and association of ribosomal subunits. The disruption of ribosome biogenesis at various steps, with either increased or decreased expression of different ribosomal components, can promote cell cycle arrest, senescence or apoptosis. Additionally, interference with ribosomal biogenesis is often associated with cancer, aging and age-related degenerative diseases. Here, we review current knowledge on impaired ribosome biogenesis, discuss the main factors involved in stress responses under such circumstances and focus on examples with clinical relevance.

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Section: Impaired Ribosome Biogenesismentioning

confidence: 99%

Impaired ribosome biogenesis: mechanisms and relevance to cancer and aging

Turi

Lacey

Mistrík

et al. 2019

Aging

165

132

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“…A second cycle was allowed, at the discretion of the investigator, in patients who achieved at least stable disease after more than 2 months. The results from these first 17 patients indicated that AS1411 was very well tolerated with no reports of any severe adverse events related to drug administration [109-111]. Also, there was evidence of clinical activity, with one patient who had metastatic renal cell carcinoma (RCC) achieving a partial response (PR) at 4 months after AS1411 treatment, which eventually became a complete response (CR) by 11 months, and an additional seven patients having disease stabilization for 2 months or more [109-111].…”

Section: Clinical Studies Of As1411mentioning

confidence: 99%

“…The results from these first 17 patients indicated that AS1411 was very well tolerated with no reports of any severe adverse events related to drug administration [109-111]. Also, there was evidence of clinical activity, with one patient who had metastatic renal cell carcinoma (RCC) achieving a partial response (PR) at 4 months after AS1411 treatment, which eventually became a complete response (CR) by 11 months, and an additional seven patients having disease stabilization for 2 months or more [109-111]. These results looked particularly promising for renal cell carcinoma, with all three of the RCC patients on this trial achieving some clinical benefit (the one patient having a CR and two additional patients having disease stabilization of ≥ 9 months duration [109-111]).…”

Section: Clinical Studies Of As1411mentioning

confidence: 99%

“…Several features of the clinical effects of AS1411 are especially interesting from a mechanistic perspective. For example, the timing of the responses (tumor shrinkage over a period of several months after a single dose of AS1411) and the duration of clinical benefit (several patients with long term disease stabilization or responses) are unusual [109-113]. …”

Section: Clinical Studies Of As1411mentioning

confidence: 99%

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Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer

Bates

Laber

Miller

et al. 2009

Experimental and Molecular Pathology

739

608

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Certain guanine-rich (G-rich) DNA and RNA molecules can associate intermolecularly or intramolecularly to form four stranded or "quadruplex" structures, which have unusual biophysical and biological properties. Several synthetic G-rich quadruplex-forming oligodeoxynucleotides have recently been investigated as therapeutic agents for various human diseases. We refer to these biologically active G-rich oligonucleotides as aptamers because their activities arise from binding to protein targets via shape-specific recognition (analogous to antibody-antigen binding). As therapeutic agents, the G-rich aptamers may have some advantages over monoclonal antibodies and other oligonucleotide-based approaches. For example, quadruplex oligonucleotides are nonimmunogenic, heat stable and they have increased resistance to serum nucleases and enhanced cellular uptake compared to unstructured sequences. In this review, we describe the characteristics and activities of G-rich oligonucleotides. We also give a personal perspective on the discovery and development of AS1411, an antiproliferative G-rich phosphodiester oligonucleotide that is currently being tested as an anticancer agent in Phase II clinical trials. This molecule functions as an aptamer to nucleolin, a multifunctional protein that is highly expressed by cancer cells, both intracellularly and on the cell surface. Thus, the serendipitous discovery of the G-rich oligonucleotides also led to the identification of nucleolin as a new molecular target for cancer therapy. KeywordsAS1411; aptamer; G-rich oligonucleotides; quadruplex; G-quartets; nucleolin; NF-kappaB; PRMT5; T-oligos; Dz13 Oligonucleotides as Therapeutic AgentsSince automated DNA synthesizers became widely available in the 1980s, there has been substantial interest in developing synthetic oligonucleotides for use as therapeutic agents [1][2][3][4][5][6][7][8][9]. Initial strategies aimed to prevent translation or transcription of specific viral or cellular * To whom correspondence should be addressed: 580 S. Preston St., Louisville, Kentucky 40202; Phone: (502) 852 2432; Email: E-mail: paula.bates@louisville.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflicts of Interest Statement:Some of the authors (PJB, JOT, DMM) are inventors of patented or patent-pending technologies related to AS1411, G-rich oligonucleotides and nucleolin. Some of the authors (PJB, JOT, DMM) are shareholders in Antisoma, the company that is now sponsoring the development of AS1411. In addition, PJB is presently a recipient of grant support from Antisoma on projects related to AS14...

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“…Besides, AGRO100 is also an aptamer that binds to nucleolin to produce anti-proliferation effects in tumor cells. In some phase I clinical trials, AGRO100 showed high safety and anti-tumor proliferation effects (Laber et al, 2004). So far, aptamers have not been approved as clinical drugs for the treatment of tumors.…”

Section: Introductionmentioning

confidence: 99%

Advances in Screening and Development of Therapeutic Aptamers Against Cancer Cells

Huang

et al. 2021

Front. Cell Dev. Biol.

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Cancer has become the leading cause of death in recent years. As great advances in medical treatment, emerging therapies of various cancers have been developed. Current treatments include surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy. Aptamers are synthetic ssDNA or RNA. They can bind tightly to target molecules due to their unique tertiary structure. It is easy for aptamers to be screened, synthesized, programmed, and chemically modified. Aptamers are emerging targeted drugs that hold great potentials, called therapeutic aptamers. There are few types of therapeutic aptamers that have already been approved by the US Food and Drug Administration (FDA) for disease treatment. Now more and more therapeutic aptamers are in the stage of preclinical research or clinical trials. This review summarized the screening and development of therapeutic aptamers against different types of cancer cells.

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A phase I study of AGRO100 in advanced cancer

Cited by 7 publications

References 0 publications

Impaired ribosome biogenesis: mechanisms and relevance to cancer and aging

Impaired ribosome biogenesis: mechanisms and relevance to cancer and aging

Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer

Advances in Screening and Development of Therapeutic Aptamers Against Cancer Cells

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