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Bacteria and Bioactive Peptides
Published in Prakash Srinivasan Timiri Shanmugam, Understanding Cancer Therapies, 2018
Ameer Khusro, Chirom Aarti, Paul Agastian
Peptides comprise a few amino acids to about 40 or more amino acids coupled through amide and/or disulfide bonds, providing varied-size molecules. In the last few years, Leuprorelin, Octreotide, and Goserelin have been used against prostate cancer and breast cancer. Carfilzomib, a protease inhibitor, is used for multiple myeloma (Kaspar and Reichert 2013). The administration of peptides can be oral, subcutaneous, intravenous, or via inhalation. In spite of limited anticancer peptides, peptide therapy may have significant potential in tumor treatment. A synthetic six amino acid peptide of αC-ß4 loop region of EGFR has been known to inhibit the dimerization and signaling activity of EGFR in the presence of its ligand (Ahsan et al. 2013). Additionally, this peptide promotes EGFR interaction with the heat shock protein Hsp90, thereby catalyzing the degradation of EGFR (Ahsan et al. 2013). At present, anticancer peptides such as Cilengitide, Trebananib, NGR-hTNF, Tyroserleutide, etc., are undergoing phase III clinical trials against glioblastoma, ovarian, mesothelioma, or liver cancers (Kaspar and Reichert 2013). The lack of targeting intracellular proteins is the major limitation of currently available anticancer peptides, thereby limiting their effectiveness (Milletti 2012). Thus, an ideal anticancer peptide involves the development of cell-penetrating peptides (CPPs) that can cross the cellular membrane to modulate key intracellular proteins involved in cancer growth regulation.
Implications of recent molecular achievements in early diagnosis and precision treatments for primary CNS lymphoma
Published in Expert Opinion on Therapeutic Targets, 2021
Teresa Calimeri, Sara Steffanoni, Marco Foppoli, Maurilio Ponzoni, Andrés J. M. Ferreri
In the last years, many efforts have been dedicated to find alternative strategies to carry chemotherapy beyond the BBB as well. In particular, ‘proof-of-principle’ results of a prospective single-arm phase II study addressing R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemoimmunotherapy preceded by low dose of an engineered human tumor necrosis factor-α (NGR-hTNF), capable of permeabilizing the BBB, in patients with r/r PCNSL were recently reported [90]. This strategy has shown excellent activity and safety profiles, providing the rationale to test this innovative strategy as first-line treatment. An alternative method to overcome the BBB could be represented by the use of nanoparticles vectoring drugs, therefore facilitating their transport to the brain tissue. However, preclinical studies are needed to evaluate the activity and tolerability of nanoparticles in murine models prior to their clinical use.
Approved and emerging treatments of malignant pleural mesothelioma in elderly patients
Published in Expert Review of Respiratory Medicine, 2019
Giovanni Luca Ceresoli, Antonio Rossi
Based on preclinical data, several targeted therapies have been explored in MPM, mainly in the second-line setting, unfortunately with discouraging results [56]. Mesothelin, a glycoprotein surface antigen, is highly expressed in MPM, mainly in the epithelioid subtype [61]. A randomized phase II trial compared anetumab ravtansine (an antibody–drug conjugate) to vinorelbine in 248 pre-treated patients; their median age was 66.5 and 65.5 years in the two groups. The study failed to demonstrate an improvement in PFS with anetumab [62]. No outcome difference was observed in younger versus elderly patients, categorized according to a cutoff of 65 years. Similar, disappointing results were reported in a very large phase III, double-blind, placebo-controlled trial with vorinostat, a histone deacetylase inhibitor that changes gene expression and protein activity [63]. NGR-hTNF, a vascular-targeting drug that increases penetration of intra-tumoral chemotherapy and T-cell infiltration by modifying the tumor microenvironment, was investigated in patients with MPM who had progressed during or after a first-line treatment. A total of 400 patients were randomized to receive NGR-hTNF in combination with best investigator choice, single-agent chemotherapy in most cases, in a phase III, double-blind, placebo-controlled trial [64]. No difference in OS between the two arms was observed. Median patient age was 65 and 67 years in the experimental and placebo arms, respectively. No difference in OS was reported according to age < or ≥65 years.
Methods for improving the immunogenicity and efficacy of cancer vaccines
Published in Expert Opinion on Biological Therapy, 2018
Lorenzo Pilla, Soldano Ferrone, Cristina Maccalli
Parmiani et al. in a phase I trial treated eight metastatic melanoma patients with a peptide vaccine associated with NGR-hTNF. NGR-hTNF allows to deliver low doses of TNF-α to the tumor vasculature and increases the permeability of tumor vasculature to lymphocytes [169]. The treatment was associated with the detection in the circulation of vaccine-specific T cells and a long-term disease control in six out of eight treated patients [169].