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The incidence of lymphoma has gradually increased over previous decades, and it ranks among the ten most prevalent cancers worldwide. With the development of targeted therapeutic strategies, though a subset of lymphoma patients has become curable, the treatment of refractory and relapsed diseases remains challenging. Many efforts have been made to explore new targets and to develop corresponding therapies. In addition to novel antibodies targeting surface antigens and small molecular inhibitors targeting oncogenic signaling pathways and tumor suppressors, immune checkpoint inhibitors and chimeric antigen receptor T-cells have been rapidly developed to target the tumor microenvironment. Although these targeted agents have shown great success in treating lymphoma patients, adverse events should be noted. The selection of the most suitable candidates, optimal dosage, and effective combinations warrant further investigation. In this review, we systematically outlined the advances in targeted therapy for malignant lymphoma, providing a clinical rationale for mechanism-based lymphoma treatment in the era of precision medicine.

Metabotropic glutamate receptor 2 (mGlu2) belongs to the group-II metabotropic glutamate (mGlu) receptors and is a neurotransmitter G protein-coupled receptor. The group-II mGlu receptors are promising antipsychotic targets, but the specific role of mGlu2 signaling remains unclear. Receptor tyrosine kinases (RTKs) are also believed to participate in brain pathogenesis. To investigate whether there is any communication between mGlu2 and RTKs, we generated a CHO-mGlu2 cell line that stably expresses mGlu2 and showed that activation of mGlu2 by LY379268, a group II mGlu agonist, was able to transactivate insulin-like growth factor 1 receptor (IGF-1R). We further determined that the G i/o protein, G βγ subunits, phospholipase C, and focal adhesion kinase (FAK) were involved in the IGF-1R transactivation signaling axis, which further induced the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and cAMP response element-binding protein. In primary mouse cortical neurons, similar signaling pathways were observed when mGlu2 were stimulated by LY487379, an mGlu2 positive allosteric modulator. Transactivation of IGF-1R through FAK in response to mGlu2 should provide a better understanding of the association of mGlu2 with brain disease.