BRAF Inhibitor Resistance in Melanoma: Mechanisms and Alternative Therapeutic Strategies.

OPINION STATEMENT: Melanoma is caused by a variety of somatic mutations, and among these mutations, BRAF mutation occurs most frequently and has routinely been evaluated as a critical diagnostic biomarker in clinical practice. The introduction of targeted agents for BRAF-mutant melanoma has significantly improved overall survival in a large proportion of patients. However, there is BRAF inhibitor resistance in most patients, and its mechanisms are complicated and need further clarification. Additionally, treatment approaches to overcome resistance have evolved rapidly, shifting from monotherapy to multimodality treatment, which has dramatically improved patient outcomes in clinical trials and practice. This review highlights the mechanisms of BRAF inhibitor resistance in melanoma and discusses the current state of its therapeutic approaches that can be further explored in clinical practice.

Median Nerve Electrical Stimulation-Induced Changes in Effective Connectivity in Patients With Stroke as Assessed With Functional Near-Infrared Spectroscopy.

Background. The cortical plastic changes in response to median nerve electrical stimulation (MNES) in stroke patients have not been entirely illustrated. Objective. This study aimed to investigate MNES-related changes in effective connectivity (EC) within a cortical network after stroke by using functional near-infrared spectroscopy (fNIRS). Methods. The cerebral oxygenation signals in the bilateral prefrontal cortex (LPFC/RPFC), motor cortex (LMC/RMC), and occipital lobe (LOL/ROL) of 20 stroke patients with right hemiplegia were measured by fNIRS in 2 conditions: (1) resting state and (2) MNES applied to the right wrist. Coupling function together with dynamical Bayesian inference was used to assess MNES-related changes in EC among the cerebral low-frequency fluctuations. Results. Compared with the resting state, EC from LPFC and RPFC to LOL was significantly increased during the MNES state in stroke patients. Additionally, MNES triggered significantly higher coupling strengths from LMC and LOL to RPFC. The interregional main coupling direction was observed from LPFC to bilateral motor and occipital areas in responding to MNES, suggesting that MNES could promote the regulation function of ipsilesional prefrontal areas in the functional network. MNES can induce muscle twitch of the stroke-affected hand involving a decreased neural coupling of the contralesional motor area on the ipsilesional MC. Conclusions. MNES can trigger sensorimotor stimulations of the affected hand that sequentially involved functional reorganization of distant cortical areas after stroke. Investigating MNES-related changes in EC after stroke may help further our understanding of the neural mechanisms underlying MNES.