title: Paradigm shift in oncology: targeting the immune system rather than cancer cells.
abstract: The clinical benefits obtained with rituximab in the treatment of CD20(+) B-cell malignancies and of imatinib in the treatment of Phi(+) leukaemias have opened a new era in oncology, transforming the concepts of tumour-targeted therapies and personalised medicine into reality. Since then, many tumour-targeted monoclonal antibodies and tyrosine kinase inhibitors have been approved for the treatment of cancers. Compared to conventional chemotherapies, these new drugs have more specificity against cancer cells and less systemic toxicities. However, like conventional chemotherapies, they often provide limited therapeutic benefits with short-lasting tumour responses as the vast majority of cancers become resistant to these drugs over time. Therefore, tumour-targeted therapies are an incremental innovation as compared to historical chemotherapies. Recently, a paradigm shift has been brought to the clinic with drugs targeting immune cells rather than cancer cells with the aim of stimulating the anti-tumour immune response of patients against their own cancer. Immunomodulatory drugs such as anti-CTLA4 and anti-PD-1 have generated long-lasting tumour responses when used as single agent in patients with refractory/relapsing cancers such as metastatic melanomas, renal cell carcinoma or non-small-cell lung carcinoma. These new immune-targeted therapies are therefore a disruptive innovation in cancer treatment: they demonstrate that long-lasting clinical benefits could be obtained by targeting molecules involved in the immune tolerance of cancer cells rather than by targeting oncogenic drivers or antigens expressed by cancer cells.
authors: Centre de Recherche en Cancérologie de Lyon, 28 Promenade Léa et Napoléon Bullukian, 69008 Lyon, France and.
authors: Tala
authors: T
authors: Shekarian
authors: Léon Bérard Comprehensive Cancer Center, 28 rue Laennec, 69008 Lyon, France.
authors: Sandrine
authors: S
authors: Valsesia-Wittmann
authors: Centre de Recherche en Cancérologie de Lyon, 28 Promenade Léa et Napoléon Bullukian, 69008 Lyon, France and.
authors: Christophe
authors: C
authors: Caux
authors: Centre de Recherche en Cancérologie de Lyon, 28 Promenade Léa et Napoléon Bullukian, 69008 Lyon, France and Léon Bérard Comprehensive Cancer Center, 28 rue Laennec, 69008 Lyon, France aurelien.marabelle@lyon.unicancer.fr.
authors: Aurélien
authors: A
authors: Marabelle
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007107:Immune System / Q000187:drug effects; D007155:Immunologic Factors / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007155:Immunologic Factors