Melanoma is the most aggressive form of skin cancer and, if spread outside the epidermis, has a dismal prognosis. Before the approval of the anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody ipilimumab and the BRAF inhibitors vemurafenib and dabrafenib, no other agents had demonstrated better results in terms of overall survival than the DNA-methylating compound dacarbazine (or its oral analog temozolomide). However, most patients with metastatic melanoma do not obtain long-lasting clinical benefit from ipilimumab and responses to BRAF inhibitors are short lived. Thus, combination therapies with inhibitors of DNA repair (e.g., poly(ADP-ribose) polymerase [PARP] inhibitors), novel immunomodulators (monoclonal antibodies against programmed death-1 [PD-1] or its ligand PD-L1), targeted therapies (mitogen-activated protein kinase [MAPK]/extracellular signal-regulated kinase [ERK] kinase [MEK] or phosphatidylinositol 3-kinase [PI3K]/AKT/mammalian target of rapamycin [mTOR] inhibitors) or antiangiogenic agents are currently being investigated to improve the efficacy of antimelanoma therapies. This review discusses the implications of simultaneously targeting key regulators of melanoma cell proliferation/survival and immune responses to counteract resistance.

Tentori, L., Lacal, P., & Graziani, G. (2013). Challenging resistance mechanisms to therapies for metastatic melanoma. TRENDS IN PHARMACOLOGICAL SCIENCES, 34(12), 656-666 [10.1016/j.tips.2013.10.003].

Challenging resistance mechanisms to therapies for metastatic melanoma

TENTORI, LUCIO;GRAZIANI, GRAZIA
2013-12

Abstract

Melanoma is the most aggressive form of skin cancer and, if spread outside the epidermis, has a dismal prognosis. Before the approval of the anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody ipilimumab and the BRAF inhibitors vemurafenib and dabrafenib, no other agents had demonstrated better results in terms of overall survival than the DNA-methylating compound dacarbazine (or its oral analog temozolomide). However, most patients with metastatic melanoma do not obtain long-lasting clinical benefit from ipilimumab and responses to BRAF inhibitors are short lived. Thus, combination therapies with inhibitors of DNA repair (e.g., poly(ADP-ribose) polymerase [PARP] inhibitors), novel immunomodulators (monoclonal antibodies against programmed death-1 [PD-1] or its ligand PD-L1), targeted therapies (mitogen-activated protein kinase [MAPK]/extracellular signal-regulated kinase [ERK] kinase [MEK] or phosphatidylinositol 3-kinase [PI3K]/AKT/mammalian target of rapamycin [mTOR] inhibitors) or antiangiogenic agents are currently being investigated to improve the efficacy of antimelanoma therapies. This review discusses the implications of simultaneously targeting key regulators of melanoma cell proliferation/survival and immune responses to counteract resistance.
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Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/14
English
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Tentori, L., Lacal, P., & Graziani, G. (2013). Challenging resistance mechanisms to therapies for metastatic melanoma. TRENDS IN PHARMACOLOGICAL SCIENCES, 34(12), 656-666 [10.1016/j.tips.2013.10.003].
Tentori, L; Lacal, P; Graziani, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/82987
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