Chemotherapy targeted to cancers through tumoral hormone receptors

Schally, Andrew V.; Nagy, Attila

doi:10.1016/j.tem.2004.07.002

Cited by 183 publications

(199 citation statements)

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“…7,8,17,22 The anti-CD20 MAb rituximab and the radiolabeled anti-CD20 antibodies Zevalin and Bexxar have shown promising clinical results in the treatment of NHL. 5,6 However, MAbs are large molecules, and it may be assumed that smaller ligands, like peptides, penetrate more easily into tumor tissue and are excreted faster if not bound to their receptor, which would decrease toxic side effects.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 However, MAbs are large molecules, and it may be assumed that smaller ligands, like peptides, penetrate more easily into tumor tissue and are excreted faster if not bound to their receptor, which would decrease toxic side effects. 8,23 Therefore, peptide hormones like somatostatin could be suitable carriers for targeted tumor therapy. 8,23 Somatostatin receptors were found in a high percentage of NHL cases, 10 indicating that chemotherapy of this malignancy could be improved by targeted cytotoxic somatostatin analogue AN-238.…”

Section: Discussionmentioning

confidence: 99%

“…8,23 Therefore, peptide hormones like somatostatin could be suitable carriers for targeted tumor therapy. 8,23 Somatostatin receptors were found in a high percentage of NHL cases, 10 indicating that chemotherapy of this malignancy could be improved by targeted cytotoxic somatostatin analogue AN-238. Selective expression of somatostatin receptor subtypes sst 2 and sst 3 in surgically removed human lymphoma specimens has been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

“…AN-238 significantly inhibits the growth of various tumors that express somatostatin receptors (subtypes 2, 3 and 5). 7,8 Here, we evaluated the antitumor effects and toxicity of cytotoxic somatostatin analogue AN-238 on 2 different human NHL cell lines xenografted in nude mice. …”

mentioning

confidence: 99%

“…5,6 In addition, receptors for some peptide hormones are found in relatively high concentrations on many cancer types, providing another option for targeted therapy with radiolabeled peptide hormones or cytotoxic peptide conjugates. [7][8][9] Expression of somatostatin receptors was found in 70 -100% of surgically removed NHL specimens of low-, intermediate-and high-grade malignancy. 10 Consequently, in several clinical studies, radiolabeled somatostatin analogues such as [ 111 In-DTPA-D-Phe 1 ]-octreotide ( 111 In-pentetreotide, OctreoScan) were used to detect lymphomatous lesions in patients with NHL.…”

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confidence: 99%

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Growth inhibition of experimental non‐Hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN‐238

Keller¹,

Engel

Schally

et al. 2005

Intl Journal of Cancer

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Key words: targeted chemotherapy; non-Hodgkin's lymphoma; somatostatin receptor; NHL is the most frequently diagnosed hematologic malignancy and ranks as the sixth most common cause of cancer-related deaths in the United States. 1,2 Over the past 50 years, an increased incidence of NHL has been reported, with an estimated 54,370 new cases in 2004. 1,2 Depending on the classification, the treatment of choice can include surgical intervention, conventional chemotherapy, radiotherapy or a combination of these. 2,3 However, patients who have advanced-stage NHL with tumors Ͼ10 cm in diameter and more than one extranodal lesion face a dismal prognosis, with a 5-year survival rate of 26%. 3 These findings emphasize the importance of developing effective therapies. 3 The discovery of specific surface antigens in various human cancers led to the development of targeted antitumor agents like MAbs. 4 These antibodies are used as single drugs or attached to radioisotopes and toxins. In the case of NHL, the anti-CD20 MAb rituximab (Rituxan) and the radiolabeled anti-CD20 antibodies Yttrium 90 ibritumomab tiuxetan (Zevalin) and 131 I tositumomab (Bexxar) were approved by the U.S. Food and Drug Administration and yielded promising clinical results. 5,6 In addition, receptors for some peptide hormones are found in relatively high concentrations on many cancer types, providing another option for targeted therapy with radiolabeled peptide hormones or cytotoxic peptide conjugates. 7-9 Expression of somatostatin receptors was found in 70 -100% of surgically removed NHL specimens of low-, intermediate-and high-grade malignancy. 10 Consequently, in several clinical studies, radiolabeled somatostatin analogues such as [ 111 In-DTPA-D-Phe 1 ]-octreotide ( 111 In-pentetreotide, OctreoScan) were used to detect lymphomatous lesions in patients with NHL. 11-14 Based on these results, the "straight" somatostatin analogue octreotide, which can decrease the growth of certain somatostatin receptor-positive cancers, was used in patients with NHL and showed some antitumor activity in 2 phase II trials when administered as a single agent or in combination therapy. 15,16 These studies [11][12][13][14][15][16] indicate that somatostatin receptors might be utilized for the targeted therapy of NHL based on radionuclide or cytotoxic somatostatin analogues.Previously, we developed a cytotoxic somatostatin analogue, AN-238, for the targeted therapy of somatostatin receptor-positive cancers. 17 AN-238 consists of the carrier somatostatin octapeptide RC-121 linked covalently to a highly potent derivate of DOX, This analogue fully retains the cytotoxic activity of the radical and binds with high affinity to somatostatin receptor subtypes sst 2 and sst 5 and with medium affinity to subtype sst 3 . AN-238 significantly inhibits the growth of various tumors that express somatostatin receptors (subtypes 2, 3 and 5). 7,8 Here, we evaluated the antitumor effects and toxicity of cytotoxic somatostatin analogue AN-238 on 2 different human NHL cell lines xenograf...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Growth inhibition of experimental non‐Hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN‐238

Keller¹,

Engel

Schally

et al. 2005

Intl Journal of Cancer

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Targeting to Peptide Receptors

Schally

Halmos

2011

Drug Delivery in Oncology

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NIR Mega‐Stokes Fluorophores for Bioorthogonal Labeling and Energy Transfer Systems–An Efficient Quencher for Daunomycin

Cserép

Enyedi

Demeter

et al. 2012

Chemistry An Asian Journal

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A set of new azide- and alkyne-bearing lepidinium-based fluorophores were synthesized for bioorthogonal labeling schemes. These fluorescent dyes all show large Stokes-shifts with emission maxima in the near-infrared (NIR) region of the electromagnetic spectrum. The applicability of these dyes in the construction of energy-transfer systems was tested using one of these new fluorescent tags and daunomycin (Dau), an anticancer drug with fluorescent features. These daunomycin conjugates are the very first examples of fluorescently modulated constructs of this anticancer agent. The dually labeled architectures proved that the applied fluorescent dye can be utilized as an efficient quencher for daunomycin. Enzymatic cleavage of a dually labeled enzyme substrate resulted in full recovery of the fluorescence of daunomycin. Such fluorescently modulated Dau conjugates can provide useful information for the mechanism of action of Dau-regulated cell death processes.

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Chemotherapy targeted to cancers through tumoral hormone receptors

Cited by 183 publications

References 50 publications

Growth inhibition of experimental non‐Hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN‐238

Growth inhibition of experimental non‐Hodgkin's lymphomas with the targeted cytotoxic somatostatin analogue AN‐238

Targeting to Peptide Receptors

NIR Mega‐Stokes Fluorophores for Bioorthogonal Labeling and Energy Transfer Systems–An Efficient Quencher for Daunomycin

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