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Cancer treatment using peptides: current therapies and future prospects.

Thundimadathil J - J Amino Acids (2012)

Bottom Line: Peptide-based hormonal therapy has been extensively studied and utilized for the treatment of breast and prostate cancers.Tremendous amount of clinical data is currently available attesting to the efficiency of peptide-based cancer vaccines.Combining immunotherapy with conventional therapies such as radiation and chemotherapy or combining an anticancer peptide with a nonpeptidic cytotoxic drug is an example of this emerging field.

View Article: PubMed Central - PubMed

Affiliation: American Peptide Company Inc., Sunnyvale, CA 94086, USA.

ABSTRACT
This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to conventional chemotherapy. Peptide can be utilized directly as a cytotoxic agent through various mechanisms or can act as a carrier of cytotoxic agents and radioisotopes by specifically targeting cancer cells. Peptide-based hormonal therapy has been extensively studied and utilized for the treatment of breast and prostate cancers. Tremendous amount of clinical data is currently available attesting to the efficiency of peptide-based cancer vaccines. Combination therapy is emerging as an important strategy to achieve synergistic effects in fighting cancer as a single method alone may not be efficient enough to yield positive results. Combining immunotherapy with conventional therapies such as radiation and chemotherapy or combining an anticancer peptide with a nonpeptidic cytotoxic drug is an example of this emerging field.

No MeSH data available.


Related in: MedlinePlus

Peptide receptor radionuclide therapy (PRRT); radiolabeled somatostatin analogs generally comprise three main parts: a cyclic octapeptide (e.g., Tyr3-octreotide or Tyr3-octreotate), a chelator (e.g., DTPA or DOTA), and a radioactive element. Radioisotopes commonly used in PRRT are 111In, 90Y, and 177Lu.
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Related In: Results  -  Collection


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fig2: Peptide receptor radionuclide therapy (PRRT); radiolabeled somatostatin analogs generally comprise three main parts: a cyclic octapeptide (e.g., Tyr3-octreotide or Tyr3-octreotate), a chelator (e.g., DTPA or DOTA), and a radioactive element. Radioisotopes commonly used in PRRT are 111In, 90Y, and 177Lu.

Mentions: Peptide receptor radionuclide therapy (PRRT) combines octreotide (or other somatostatin analogs) with a radionuclide (a radioactive substance) to form highly specialized molecules called radiolabeled somatostatin analogues or radiopeptides [39–48]. Radiolabeled somatostatin analogs generally comprise three main parts: a cyclic octapeptide (e.g., octreotide), a chelator (e.g., DTPA or DOTA), and a radioactive element (111In, 90Y, or 177Lu). These radiopeptides can be injected into a patient and will travel throughout the body binding to carcinoid tumor cells that have receptors for them. Once bound, these radiopeptides emit radiation and kill the tumor cells they are bound to (Figure 2). PRRT using [111In-DTPA]-octreotide (where DTPA is diethylenetriamine pentaacetic acid) is feasible because, besides gamma radiation, 111In emits both therapeutic Auger and internal conversion electrons having tissue penetration ability [39, 40]. However, studies have shown that 111In-coupled peptides are not efficient for PRRT, as the short distance traveled by Auger electrons after emission means that decay of 111In has to occur close to the cell nucleus to be tumoricidal [39, 40]. It was found that replacement of phenylalanine by tyrosine as the third amino acid in the octapeptide leads to an increased affinity for somatostatin-receptor subtype 2. This resulted in the development of next generation therapy using 90Y-DOTA, Tyr3-octreotide [41–44]. This compound has DOTA (tetraazacyclododecane tetraacetic acid) instead of DTPA as the chelator, which allows stable binding of 90Y, a β-emitting radionuclide. Various clinical trials around the world showed that it is better than [111In-DTPA]-octreotide in treating gastroenteropancreatic neuroendocrine tumors (GEPNETs). A third generation of somatostatin-receptor-targeted radionuclide therapies was introduced using 177Lu-DOTA, Tyr3-octreotate [49, 50]. The only difference between DOTA, Tyr3-octreotate and DOTA, Tyr3-octreotide is that the C-terminal threoninol of DOTA, Tyr3-octreotide is replaced with the amino acid, threonine. As a result, DOTA, Tyr3-octreotate displays improved binding to somatostatin-receptor-positive tissues when compared with DOTA, Tyr3-octreotide [49]. Gastroenteropancreatic tumors predominantly express subtype 2 of the somatostatin receptor, and DOTA, Tyr3-octreotate has a sixfold to ninefold increased affinity for this receptor subtype in vitro compared with DOTA, Tyr3-octreotide [43, 49, 50]. 177Lu-octreotate was very successful in terms of tumor regression and survival in an experimental model in rats. 177Lu-labeled somatostatin analogs have an important practical advantage over their 90Y-labeled counterparts: 177Lu is not a pure β emitter, but also emits low-energy γ rays, which allows direct posttherapy imaging and dosimetry. Treatment with 177Lu-octreotate resulted in a survival benefit of several years and markedly improved quality of life. PRRT might soon become the therapy of choice for patients with metastatic or inoperable GEPNETs. Nowadays, different somatostatin analogs are available not only for therapeutic purposes but also when labeled with b1-emitters (e.g., 68Ga and 64Cu) for tumor imaging with integrated PET/CT scanners [51, 52]. The PET/CT technology provides a highly valuable combination of physiologic and anatomic information and has been shown to impact significantly on the patient's management.


Cancer treatment using peptides: current therapies and future prospects.

Thundimadathil J - J Amino Acids (2012)

Peptide receptor radionuclide therapy (PRRT); radiolabeled somatostatin analogs generally comprise three main parts: a cyclic octapeptide (e.g., Tyr3-octreotide or Tyr3-octreotate), a chelator (e.g., DTPA or DOTA), and a radioactive element. Radioisotopes commonly used in PRRT are 111In, 90Y, and 177Lu.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539351&req=5

fig2: Peptide receptor radionuclide therapy (PRRT); radiolabeled somatostatin analogs generally comprise three main parts: a cyclic octapeptide (e.g., Tyr3-octreotide or Tyr3-octreotate), a chelator (e.g., DTPA or DOTA), and a radioactive element. Radioisotopes commonly used in PRRT are 111In, 90Y, and 177Lu.
Mentions: Peptide receptor radionuclide therapy (PRRT) combines octreotide (or other somatostatin analogs) with a radionuclide (a radioactive substance) to form highly specialized molecules called radiolabeled somatostatin analogues or radiopeptides [39–48]. Radiolabeled somatostatin analogs generally comprise three main parts: a cyclic octapeptide (e.g., octreotide), a chelator (e.g., DTPA or DOTA), and a radioactive element (111In, 90Y, or 177Lu). These radiopeptides can be injected into a patient and will travel throughout the body binding to carcinoid tumor cells that have receptors for them. Once bound, these radiopeptides emit radiation and kill the tumor cells they are bound to (Figure 2). PRRT using [111In-DTPA]-octreotide (where DTPA is diethylenetriamine pentaacetic acid) is feasible because, besides gamma radiation, 111In emits both therapeutic Auger and internal conversion electrons having tissue penetration ability [39, 40]. However, studies have shown that 111In-coupled peptides are not efficient for PRRT, as the short distance traveled by Auger electrons after emission means that decay of 111In has to occur close to the cell nucleus to be tumoricidal [39, 40]. It was found that replacement of phenylalanine by tyrosine as the third amino acid in the octapeptide leads to an increased affinity for somatostatin-receptor subtype 2. This resulted in the development of next generation therapy using 90Y-DOTA, Tyr3-octreotide [41–44]. This compound has DOTA (tetraazacyclododecane tetraacetic acid) instead of DTPA as the chelator, which allows stable binding of 90Y, a β-emitting radionuclide. Various clinical trials around the world showed that it is better than [111In-DTPA]-octreotide in treating gastroenteropancreatic neuroendocrine tumors (GEPNETs). A third generation of somatostatin-receptor-targeted radionuclide therapies was introduced using 177Lu-DOTA, Tyr3-octreotate [49, 50]. The only difference between DOTA, Tyr3-octreotate and DOTA, Tyr3-octreotide is that the C-terminal threoninol of DOTA, Tyr3-octreotide is replaced with the amino acid, threonine. As a result, DOTA, Tyr3-octreotate displays improved binding to somatostatin-receptor-positive tissues when compared with DOTA, Tyr3-octreotide [49]. Gastroenteropancreatic tumors predominantly express subtype 2 of the somatostatin receptor, and DOTA, Tyr3-octreotate has a sixfold to ninefold increased affinity for this receptor subtype in vitro compared with DOTA, Tyr3-octreotide [43, 49, 50]. 177Lu-octreotate was very successful in terms of tumor regression and survival in an experimental model in rats. 177Lu-labeled somatostatin analogs have an important practical advantage over their 90Y-labeled counterparts: 177Lu is not a pure β emitter, but also emits low-energy γ rays, which allows direct posttherapy imaging and dosimetry. Treatment with 177Lu-octreotate resulted in a survival benefit of several years and markedly improved quality of life. PRRT might soon become the therapy of choice for patients with metastatic or inoperable GEPNETs. Nowadays, different somatostatin analogs are available not only for therapeutic purposes but also when labeled with b1-emitters (e.g., 68Ga and 64Cu) for tumor imaging with integrated PET/CT scanners [51, 52]. The PET/CT technology provides a highly valuable combination of physiologic and anatomic information and has been shown to impact significantly on the patient's management.

Bottom Line: Peptide-based hormonal therapy has been extensively studied and utilized for the treatment of breast and prostate cancers.Tremendous amount of clinical data is currently available attesting to the efficiency of peptide-based cancer vaccines.Combining immunotherapy with conventional therapies such as radiation and chemotherapy or combining an anticancer peptide with a nonpeptidic cytotoxic drug is an example of this emerging field.

View Article: PubMed Central - PubMed

Affiliation: American Peptide Company Inc., Sunnyvale, CA 94086, USA.

ABSTRACT
This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to conventional chemotherapy. Peptide can be utilized directly as a cytotoxic agent through various mechanisms or can act as a carrier of cytotoxic agents and radioisotopes by specifically targeting cancer cells. Peptide-based hormonal therapy has been extensively studied and utilized for the treatment of breast and prostate cancers. Tremendous amount of clinical data is currently available attesting to the efficiency of peptide-based cancer vaccines. Combination therapy is emerging as an important strategy to achieve synergistic effects in fighting cancer as a single method alone may not be efficient enough to yield positive results. Combining immunotherapy with conventional therapies such as radiation and chemotherapy or combining an anticancer peptide with a nonpeptidic cytotoxic drug is an example of this emerging field.

No MeSH data available.


Related in: MedlinePlus