TTI-101: A competitive inhibitor of STAT3 that spares oxidative phosphorylation and reverses mechanical allodynia in mouse models of neuropathic pain.

Signal Transducer and Activator of Transcription (STAT) 3 emerged rapidly as a high-value target for treatment of cancer. However, small-molecule STAT3 inhibitors have been slow to enter the clinic due, in part, to serious adverse events (SAE), including lactic acidosis and peripheral neuropathy, which have been attributed to inhibition of STAT3's mitochondrial function. Our group developed TTI-101, a competitive inhibitor of STAT3 that targets the receptor pY705-peptide binding site within the Src homology 2 (SH2) domain to block its recruitment and activation. TTI-101 has shown target engagement, no toxicity, and evidence of clinical benefit in a Phase I study in patients with solid tumors. Here we report that TTI-101 did not affect mitochondrial function, nor did it cause STAT3 aggregation, chemically modify STAT3 or cause neuropathic pain. Instead, TTI-101 unexpectedly suppressed neuropathic pain induced by chemotherapy or in a spared nerve injury model. Thus, in addition to its direct anti-tumor effect, TTI-101 may be of benefit when administered to cancer patients at risk of developing chemotherapy-induced peripheral neuropathy (CIPN).

We are All Leaders: Introducing Self-Leadership Concepts Through the Lens of Improving Diversity in the Health Care Workforce.

Introduction: Increasing faculty and leader diversity has been recommended as a way for health care organizations to achieve cultural competence in their patient care mission. Given the low numbers of underrepresented groups in medical school leadership positions, teaching diverse students and trainees the concept of leadership as influence may empower them to become more involved and bring diverse perspectives to their organizations. Methods: This 70-minute workshop consisted of a short presentation, a self-assessment, small- and large-group discussions, and case studies to: (1) describe the importance of diversity in medical school leadership, (2) define leadership, (3) define self-leadership, and (4) assess one's own self-leadership skills. The workshop was implemented at three US medical schools to diverse medical students and residents between September and December of 2019. Pre- and postworkshop evaluations were analyzed. Results: Greater than 95% of learners (n = 66) agreed that the workshop's learning objectives were met. Comments suggested participants appreciated learning about the lack of diversity among medical school leaders and the importance of cultivating their role in diversity in academic medicine. The case studies were highly rated and considered effective tools for learning. Discussion: This submission defined an empowering notion of leadership as influence. It taught learners that we can all lead (by influence) if we can improve our own self-leadership skills and become involved and bring diverse perspectives to health care organizations. Future research may focus on longer-term follow-up of participants to reassess their self-leadership skills and describe their level of involvement in their organizations.