Rethinking Alkylating(-Like) Agents for Solid Tumor Management

Hélène Lajous (1, 2) , Bénédicte Lelièvre (3) , Elodie Vauleon (4, 5) , Philippe Lecomte (1) , Emmanuel Garcion (2)

1 Université de Liège
2 CRCINA-ÉQUIPE 17 - Design and Application of Innovative Local Treatments in Glioblastoma
3 CHU Angers - Centre Hospitalier Universitaire d'Angers
4 COSS - Chemistry, Oncogenesis, Stress and Signaling
5 CRLCC - CRLCC Eugène Marquis

Although old molecules, alkylating agents and platinum derivatives are still widely used in the treatment of various solid tumors. However, systemic toxicity and cellular resistance mechanisms impede their efficacy. Innovative strategies, including local administration, optimization of treatment schedule/dosage, synergistic combinations, and the encapsulation of bioactive molecules in smart, multifunctional drug delivery systems, have shown promising results in potentiating anticancer activity while circumventing such hurdles. Furthermore, questioning of the old paradigm according to which nuclear DNA is the critical target of their anticancer activity has shed light on subcellular alternative and neglected targets that obviously participate in the mediation of cytotoxicity or resistance. Thus, rethinking of the use of these pivotal antineoplastic agents appears critical to improve clinical outcomes in the management of solid tumors.

Mots clés: local treatment; cisplatin; alkylating agents; synergies; solid tumors; nanomedicine

Domaines: Cancer

Hélène Lajous, Bénédicte Lelièvre, Elodie Vauleon, Philippe Lecomte, Emmanuel Garcion. Rethinking Alkylating(-Like) Agents for Solid Tumor Management. Trends in Pharmacological Sciences, 2019, 40 (5), pp.342-357. ⟨10.1016/j.tips.2019.03.003⟩. ⟨hal-02121104⟩