A randomized phase II trial of interleukin-2 in combination with four different doses of bryostatin-1 in patients with renal cell carcinoma

Peterson, Amy; Harlin, Helena; Karrison, Theodore; Vogelzang, Nicholas J.; Knost, James A.; Kugler, John W.; Lester, Eric P.; Vokes, Everett E.; Gajewski, Thomas F.; Stadler, Walter M.

doi:10.1007/s10637-006-5935-4

Cited by 16 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bryostatin-1, a PKC modulator that targets the C1 domain, is the most extensively used in clinical trials. Recent phase II clinical trials with bryostatin-1 in combination with cisplatin for cervical squamous cell carcinoma or in combination with interleukin-2 for renal cell carcinoma showed minimal efficacy and perhaps even a possibility of therapeutic antagonism (12, 13). One possible explanation is that C1 domain inhibitors are not isoform specific since the C1 domain is well conserved in the PKC family, with the exception of the atypical isoforms.…”

Section: Resultsmentioning

confidence: 99%

Preclinical Development of a Bifunctional Cancer Cell Homing, PKCε Inhibitory Peptide for the Treatment of Head and Neck Cancer

et al. 2009

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide, comprising f50% of all malignancies in some developing nations. Our recent work identified protein kinase CE (PKCE) as a critical and causative player in establishing an aggressive phenotype in HNSCC. In this study, we investigated the specificity and efficacy of HN1-PKCE, a novel bifunctional cancer cell homing, PKCE inhibitory peptide, as a treatment for HNSCC. HN1-PKCE peptide was designed by merging two separate technologies and synthesized as a capped peptide with two functional modules, HN1 (cancer cell homing) and PKCE (specific PKCE inhibitory), connected by a novel linker module. HN1-PKCE preferentially internalized into UMSCC1 and UMSCC36 cells, two HNSCC cell lines, in comparison with oral epithelial cells: 82.1% positive for UMSCC1 and 86.5% positive for UMSCC36 compared with 1.2% positive for oral epithelial cells. In addition, HN1-PKCE penetrated HNSCC cells in a dose-and time-dependent manner. Consistent with these in vitro observations, systemic injection of HN1-PKCE resulted in selective delivery of HN1-PKCE into UMSCC1 xenografts in nude mice. HN1-PKCE blocked the translocation of active PKCE in UMSCC1 cells, confirming HN1-PKCE as a PKCE inhibitor. HN1-PKCE inhibited cell invasion by 72 F 2% (P < 0.001, n = 12) and cell motility by 56 F 2% (P < 0.001, n = 5) in UMSCC1 cells. Moreover, in vivo bioluminescence imaging showed that HN1-PKCE significantly (83 F 1% inhibition; P < 0.02) retards the growth of UMSCC1 xenografts in nude mice. Our work indicates that the bifunctional HN1-PKCE inhibitory peptide represents a promising novel therapeutic strategy for

show abstract

Section: Resultsmentioning

confidence: 99%

Preclinical Development of a Bifunctional Cancer Cell Homing, PKCε Inhibitory Peptide for the Treatment of Head and Neck Cancer

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Different types of human cancers have been investigated in these clinical studies, including chronic lymphocytic leukemia, non-Hodgkin lymphoma, multiple myeloma, melanoma, renal cell carcinoma, colorectal cancer, soft tissue sarcoma, head and neck cancer, ovarian cancer, cervix carcinoma, gastric cancer, gastroesophageal cancer, esophageal cancer and pancreatic carcinoma [79,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150]. From the results of its clinical trials, several important conclusions can be drawn: ( 1 ) Myalgia is its main human dose-limiting toxicity with the occurrence of 10%–87.5% found in phase II trials [151].…”

Section: Clinical Trials Of Marine-derived Angiogenesis Inhibitorsmentioning

confidence: 99%

Marine-Derived Angiogenesis Inhibitors for Cancer Therapy

Wang

Miao

2013

Marine Drugs

View full text Add to dashboard Cite

Angiogenesis inhibitors have been successfully used for cancer therapy in the clinic. Many marine-derived natural products and their analogues have been reported to show antiangiogenic activities. Compared with the drugs in the clinic, these agents display interesting characteristics, including diverse sources, unique chemical structures, special modes of action, and distinct activity and toxicity profiles. This review will first provide an overview of the current marine-derived angiogenesis inhibitors based on their primary targets and/or mechanisms of action. Then, the marine-derived antiangiogenic protein kinase inhibitors will be focused on. And finally, the clinical trials of the marine-derived antiangiogenic agents will be discussed, with special emphasis on their application potentials, problems and possible coping strategies in their future development as anticancer drugs.

show abstract

“…In fact, an upregulation of IL2 by PKC has been reported and a phase II study was conducted combining IL2 with bryostatin 1 in patients with renal cell carcinoma. Although it was well tolerated, the addition of bryostatin 1 did not appear to improve response rates and there was no significant effect on T-cell expansion, activation or cytokine production [232]. Given that bryostatin has pleiotropic effects, it is not clear which are the most promising targets to measure in terms of predicting anticancer activity in any given tumor type.…”

Section: Pkc Modulators: From the Laboratory To Its Clinical Employmentmentioning

confidence: 99%

Protein Kinase C: An Attractive Target for Cancer Therapy

Marengo

Ciucis

Ricciarelli

et al. 2011

Cancers

View full text Add to dashboard Cite

Apoptosis plays an important role during all stages of carcinogenesis and the development of chemoresistance in tumor cells may be due to their selective defects in the intracellular signaling proteins, central to apoptotic pathways. Consequently, many studies have focused on rendering the chemotherapy more effective in order to prevent chemoresistance and pre-clinical and clinical data has suggested that protein kinase C (PKC) may represent an attractive target for cancer therapy. Therefore, a complete understanding of how PKC regulates apoptosis and chemoresistance may lead to obtaining a PKC-based therapy that is able to reduce drug dosages and to prevent the development of chemoresistance.

show abstract

A randomized phase II trial of interleukin-2 in combination with four different doses of bryostatin-1 in patients with renal cell carcinoma

Abstract: The addition of Bryostatin-1 to IL-2 was well tolerated, but the overall response rate was low (3.2%), indicating that further studies with this combination are not warranted.

Cited by 16 publications

References 32 publications

Preclinical Development of a Bifunctional Cancer Cell Homing, PKCε Inhibitory Peptide for the Treatment of Head and Neck Cancer

Preclinical Development of a Bifunctional Cancer Cell Homing, PKCε Inhibitory Peptide for the Treatment of Head and Neck Cancer

Marine-Derived Angiogenesis Inhibitors for Cancer Therapy

Protein Kinase C: An Attractive Target for Cancer Therapy

Contact Info

Product

Resources

About