Mantle cell lymphoma: insights into therapeutic targets at the preclinical level

Mantle cell lymphoma (MCL) is a chronically relapsing B-cell non-Hodgkin lymphoma characterized by recurrent molecular-cytogenetic aberrations that lead to deregulation of DNA damage response, cell cycle progression, epigenetics, apoptosis, proliferation, and motility. In the last 10 years, clinical approval of several innovative drugs dramatically changed the landscape of treatment options in the relapsed/refractory (R/R) MCL, which translated into significantly improved survival parameters.

Here, up-to-date knowledge on the biology of MCL together with currently approved and clinically tested frontline and salvage therapies are reviewed. In addition, novel therapeutic targets in MCL based on the scientific reports published in Pubmed are discussed.

Bruton tyrosine-kinase inhibitors, NFkappaB inhibitors, BCL2 inhibitors, and immunomodulary agents in combination with monoclonal antibodies and genotoxic drugs have the potential to induce long-term remissions in majority of newly diagnosed MCL patients. Several other classes of anti-tumor drugs including phosphoinositole-3-kinase, cyclin-dependent kinase or DNA damage response kinase inhibitors have demonstrated promising anti-lymphoma efficacy in R/R MCL. Most importantly, adoptive immunotherapy with genetically modified T-cells carrying chimeric antigen receptor represents a potentially curative treatment approach even in the patients with chemotherapy and ibrutinib-refractory disease.