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Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in colorectal cancer preclinical models with a preferential effect in p53-mutant cell lines linked with direct binding of p53 to repeat elements. We translate these findings to a human phase II trial of single-agent 3TC treatment in metastatic colorectal cancer with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on colorectal cancer tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage response. Epigenetic and DNA-damaging agents induce repeat RNAs and have enhanced cytotoxicity with 3TC. These findings identify a vulnerability in colorectal cancer by targeting the viral mimicry of repeat elements.Significance:Colorectal cancers express abundant repeat elements that have a viral-like life cycle that can be therapeutically targeted with nucleoside reverse transcriptase inhibitors (NRTI) commonly used for viral diseases. NRTIs induce DNA damage and interferon response that provide a new anticancer therapeutic strategy.This article is highlighted in the In This Issue feature, p. 1397

Supplementary Figure from Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Supplementary Data from Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in colorectal cancer preclinical models with a preferential effect in p53-mutant cell lines linked with direct binding of p53 to repeat elements. We translate these findings to a human phase II trial of single-agent 3TC treatment in metastatic colorectal cancer with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on colorectal cancer tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage response. Epigenetic and DNA-damaging agents induce repeat RNAs and have enhanced cytotoxicity with 3TC. These findings identify a vulnerability in colorectal cancer by targeting the viral mimicry of repeat elements.Significance:Colorectal cancers express abundant repeat elements that have a viral-like life cycle that can be therapeutically targeted with nucleoside reverse transcriptase inhibitors (NRTI) commonly used for viral diseases. NRTIs induce DNA damage and interferon response that provide a new anticancer therapeutic strategy.This article is highlighted in the In This Issue feature, p. 1397

At our institution, we aim to foster interest in oncology through the Student Oncology Society (SOS). The SOS was formed in 2010 and since then has hosted numerous oncology-related events, such as career panels, patient survivorship celebrations, and movie screenings. The purpose of this study is to report the experiences from former student leaders of the SOS, particularly how their participation informed their career choice. Complete survey responses were obtained from 26 of 32 former SOS student leaders (response rate 81.3%). Out of the 26 respondents, 19 (73.1%) are pursuing an oncology-related specialty. The three most common competencies that were affected by participation in SOS, noted by 21 (80.8%) respondents, were learning about pathways to careers in oncology, understanding the multidisciplinary approach to cancer care, and coordinating events. By mean Likert score, the most important factors in career choice for respondents who eventually pursued an oncology field were having a mentor in oncology (4.44), a clinical rotation in oncology (4.31), research involvement (4.22), and SOS involvement (3.17). While SOS involvement played a role in career choice among our student leaders, having a mentor was cited to be the most important factor for choosing an oncology career. Thus, implementation of formal mentorship initiatives within the framework of oncology interest groups should be explored.