Platinum-based chemotherapeutic drugs are front-line therapies for the treatment of non-small cell lung cancer. However, intrinsic drug resistance limits the clinical efficacy of these agents. Recent evidence suggests that loss of the translesion polymerase, Polζ, can sensitize tumor cell lines to cisplatin, although the relevance of these findings to the treatment of chemoresistant tumors in vivo has remained unclear. Here, we describe a tumor transplantation approach that enables the rapid introduction of defined genetic lesions into a preclinical model of lung adenocarcinoma. Using this approach, we examined the effect of impaired translesion DNA synthesis on cisplatin response in aggressive late-stage lung cancers. In the presence of reduced levels of Rev3, an essential component of Polζ, tumors exhibited pronounced sensitivity to cisplatin, leading to a significant extension in overall survival of treated recipient mice. Additionally, treated Rev3-deficient cells exhibited reduced cisplatin-induced mutation, a process that has been implicated in the induction of secondary malignancies following chemotherapy. Taken together, our data illustrate the potential of Rev3 inhibition as an adjuvant therapy for the treatment of chemoresistant malignancies, and highlight the utility of rapid transplantation methodologies for evaluating mechanisms of chemotherapeutic resistance in preclinical settings.

The COVID-19 pandemic has had a profound impact on the nation's health care system, including on graduate medical education (GME) training programs. Traditionally, residency and fellowship training program applications involve in-person interviews conducted on-site, with only a minority of programs offering interviews remotely via a virtual platform. However, in light of the COVID-19 pandemic, it is anticipated that most interviews will be conducted virtually for the 2021 application cycle and possibly beyond. Therefore, GME Please see the end of this article for information about the authors.

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Due to the COVID-19 pandemic, most graduate medical education (GME) training programs conducted virtual interviews for prospective trainees during the 2020-2021 application cycle. Many internal medicine (IM) subspecialty fellowship programs hosted virtual interviews for the first time with little published data to guide best practices.To evaluate how IM subspecialty fellowship applicants perceived the virtual interview day experience.We designed a 38-item questionnaire that was sent via email to applicants in eight IM subspecialty programs at a single tertiary academic medical center (University of California, San Francisco) from September-November, 2020.Seventy-five applicants completed the survey (75/244, 30.7%), including applicants from all eight fellowship programs. Most survey respondents agreed that the length of the virtual interview day (mean = 6.4 hours) was long enough to gather the information they needed (n = 65, 86.7%) and short enough to prevent fatigue (n = 55, 73.3%). Almost all survey respondents agreed that they could adequately assess the clinical experience (n = 71, 97.3%), research opportunities (n = 72, 98.6%), and program culture (n = 68, 93.2%). Of the respondents who attended a virtual educational conference, most agreed it helped to provide a sense of the program's educational culture (n = 20, 66.7%). Areas for improvement were identified, with some survey respondents reporting that the virtual interview day was too long (n = 11) or that they would have preferred to meet more fellows (n = 10).Survey respondents indicated that the virtual interview was an adequate format to learn about fellowship programs. These findings can inform future virtual interviews for GME training programs.

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