Depletion of nerve growth factor in chemotherapy-induced peripheral neuropathy associated with hematologic malignancies

Abstract

ObjectiveTo investigate whether the depletion of nerve growth factor (NGF) is associated with the development of chemotherapy-induced peripheral neuropathy (CIPN) in patients with hematologic malignancy.MethodsWe prospectively enrolled hematologic cancer patients who had a plan to receive bortezomib, thalidomide, or vincristine. Baseline NGF levels were measured within one week before the start date of chemotherapy. Follow-up NGF levels were measured after four months from the start date of chemotherapy or the date when CIPN was initially diagnosed.ResultsBaseline and follow-up NGF pairs were measured in 45 patients (male/female = 27/18, median age = 63 years old). CIPN has developed in 28 patients. In the CIPN group, the level of NGF was significantly decreased after chemotherapy compared to the baseline (△NGF = −3.52 ±5.72; p-value = 0.003), while the NGF level of the no-CIPN group was not changed after chemotherapy. The differences in △NGF levels between the CIPN and no-CIPN group were more profound when analyzed in the subgroup of newly diagnosed multiple myeloma patients (△NGF = −4.14 ± 4.87 pg/ml for the CIPN group and +2.52 ± 8.39 pg/ml for the no-CIPN group; p-value = 0.043).ConclusionsThis study shows that the depletion of NGF occurs during the development of CIPN, suggesting pathogenesis based on the role of NGF and therapeutic implications.

Chemotherapy‐induced peripheral neuropathy: Identifying the research gaps and associated changes to clinical trial design

“…The second most common chemotherapy studies were platinum‐based compounds, with more studies investigating oxaliplatin 23,24,31,34,35,39,62‐72 than cisplatin 26,35,40,49,73‐82 . Studies less often involved bortezomib 24,26,67,83‐94 and vincristine 42,45,50,54,84,93,95‐101 . Only 2 studies investigated thalidomide‐induced neuropathy when used in combination with other anticancer agents 84,93 .…”

“…Studies less often involved bortezomib 24,26,67,83‐94 and vincristine 42,45,50,54,84,93,95‐101 . Only 2 studies investigated thalidomide‐induced neuropathy when used in combination with other anticancer agents 84,93 . A total of 23 studies explored new molecular compounds (eg, nerve growth factor) or agents approved for other purposes (eg, retigabine) to mitigate the development or progression of CIPN.…”

“…Among the clinical studies (12%), the majority (8 clinical studies) included taxane‐based therapies 36,39,40,45,49,61,62,102 . Other therapies included vincristine, 45,84,93 cisplatin, 40,49 oxaliplatin, 39,61 bortezomib, 84,93 and thalidomide 84,93 . Two of these studies explored inflammation‐related biomarkers, 36,39 and other studies examined mechanisms related to neuropathy such as nerve growth factor, 40,93 epidermal nerve fibers, 45,61 and axonal damage 40,62 .…”

“…Other therapies included vincristine, 45,84,93 cisplatin, 40,49 oxaliplatin, 39,61 bortezomib, 84,93 and thalidomide 84,93 . Two of these studies explored inflammation‐related biomarkers, 36,39 and other studies examined mechanisms related to neuropathy such as nerve growth factor, 40,93 epidermal nerve fibers, 45,61 and axonal damage 40,62 . These studies using human subjects involved collecting blood samples or observing the brain scans of patients, including those within certain subgroups such as patients with lung cancer, 40 multiple myeloma, 84 breast cancer, 36,49 or hematologic cancer 93 .…”

Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

“…The correlation between a reduced NGF level and the occurrence of diabetic neuropathy has been well documented (Anand et al, ). Indeed, depletion of NGF occurs during the development of CIPN (Youk et al, ), possibly by increased oxidative stress (Hounsom, Corder, Patel, & Tomlinson, ), which in turn activates proinflammatory mediators and apoptosis (Flatters & Bennett, ; Luedde & Schwabe, ). Transplanted MSCs not only directly differentiate into neurons and endothelial cells but also secrete a number of biologically active factors, such as fibroblast growth factor (FGF), VEGF‐A, and NGF, which are central to neuronal and vascular tissues health (Hsieh et al, ; Quertainmont et al, ).…”