Elesclomol (formerly STA-4783) is a novel small molecule undergoing clinical evaluation in a pivotal phase III melanoma trial (SYMMETRY). In a phase II randomized, double-blinded, controlled, multi-center trial in 81 patients with stage IV metastatic melanoma, treatment with elesclomol plus paclitaxel showed a statistically significant doubling of progression-free survival time compared with treatment with paclitaxel alone. Although elesclomol displays significant therapeutic activity in the clinic, the mechanism underlying its anticancer activity has not been defined previously. Here, we show that elesclomol induces apoptosis in cancer cells through the induction of oxidative stress. Treatment of cancer cells in vitro with elesclomol resulted in the rapid generation of reactive oxygen species (ROS) and the induction of a transcriptional gene profile characteristic of an oxidative stress response. Inhibition of oxidative stress by the antioxidant N-acetylcysteine blocked the induction of gene transcription by elesclomol. In addition, N-acetylcysteine blocked drug-induced apoptosis, indicating that ROS generation is the primary mechanism responsible for the proapoptotic activity of elesclomol. Excessive ROS production and elevated levels of oxidative stress are critical biochemical alterations that contribute to cancer cell growth. Thus, the induction of oxidative stress by elesclomol exploits this unique characteristic of cancer cells by increasing ROS levels beyond a threshold that triggers cell death.

Graphene near charge neutrality is expected to behave like a quantum-critical, relativistic plasma—the “Dirac fluid”—in which massless electrons and holes rapidly collide at a rapid rate. We measure the frequency-dependent optical conductivity of clean, micron-scale graphene at electron temperatures between 77 and 300 K using on-chip terahertz spectroscopy. At charge neutrality, we observe the quantum-critical scattering rate characteristic of the Dirac fluid. At higher doping, we uncover two distinct current-carrying modes with zero and nonzero total momenta, a manifestation of relativistic hydrodynamics. Our work reveals the quantum criticality and unusual dynamic excitations near charge neutrality in graphene.

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