Surmounting Chemotherapy and Radioresistance in Chondrosarcoma: Molecular Mechanisms and Therapeutic Targets

Chondrosarcoma, a primary malignancy of bone, has eluded successful treatment with modern chemotherapeutic and radiation regimens. To date, surgical resection of these tumors remains the only curative treatment offered to patients with this diagnosis. Understanding and exploring the nature of chemotherapy and radiation resistance in chondrosarcoma could lead to new molecular targets and more directed therapy for these notoriously difficult-to-treat tumors. Here we review the most current hypotheses regarding the molecular mechanisms mediating chemotherapy and radiation resistance and the future direction of chondrosarcoma therapy research

Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: A randomized, placebo-controlled, crossover study

Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of a2d subunits of voltage-gated Ca21 channels, such as pregabalin, have shown efficacy in reducing mechanical sensitivity in animal models of neuropathic pain. In addition, some data suggest that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased sensitivity to pinprick. We hypothesized that greater mechanical sensitivity, as quantified by decreased mechanical pain threshold at the feet, would be predictive of a greater reduction in average daily pain in response to pregabalin vs placebo. In a prospective, randomized, double-blinded study, 26 patients with painful CIPN from oxaliplatin, docetaxel, or paclitaxel received 28-day treatment with pregabalin (titrated to maximum dose 600 mg per day) and placebo in crossover design. Twenty-three participants were eligible for efficacy analysis. Mechanical pain threshold was not significantly correlated with reduction in average pain (P 5 0.97) or worst pain (P 5 0.60) in response to pregabalin. There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, P 5 0.23) or worst pain (29.2% vs 16.0%, P 5 0.13) from baseline. Post hoc analysis of patients with CIPN caused by oxaliplatin (n 5 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, P 5 0.04). In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN