Management of Drug Resistance in Mantle Cell Lymphoma

Gaël Roué (1) , Brigitte Sola (2)

1 Vall d'Hebron University Hospital [Barcelona]
2 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques

Mantle cell lymphoma (MCL) is a rare but aggressive B-cell hemopathy characterized by the translocation t(11;14)(q13;q32) that leads to the overexpression of the cell cycle regulatory protein cyclin D1. This translocation is the initial event of the lymphomagenesis, but tumor cells can acquire additional alterations allowing the progression of the disease with a more aggressive phenotype and a tight dependency on microenvironment signaling. To date, the chemotherapeutic-based standard care is largely inefficient and despite the recent advent of different targeted therapies including proteasome inhibitors, immunomodulatory drugs, tyrosine kinase inhibitors, relapses are frequent and are generally related to a dismal prognosis. As a result, MCL remains an incurable disease. In this review, we will present the molecular mechanisms of drug resistance learned from both preclinical and clinical experiences in MCL, detailing the main tumor intrinsic processes and signaling pathways associated to therapeutic drug escape. We will also discuss the possibility to counteract the acquisition of drug refractoriness through the design of more efficient strategies, with an emphasis on the most recent combination approaches.

Mots clés: combinatory treatment; therapeutic strategy; B-cell lymphoma; cyclin D1; proteasome inhibitor; ibrutinib; NF-kB pathway; mutation; innate resistance; acquired resistance

Domaines: Organisation et fonctions cellulaires [q-bio.SC]; Interactions cellulaires [q-bio.CB]; Cancer

Gaël Roué, Brigitte Sola. Management of Drug Resistance in Mantle Cell Lymphoma. Cancers, 2020, 12, ⟨10.3390/cancers12061565⟩. ⟨hal-02866782⟩