PubMed · 7110096
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G Neretto. [Bladder tumors].. https://pubmed.ncbi.nlm.nih.gov/7110096/
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Drug response differs substantially in cancer patients due to inter- and intra-tumor heterogeneity. Particularly, transcriptome context, especially tumor microenvironment, has been shown playing a significant role in shaping the actual treatment outcome. In this study, we develop a deep variational autoencoder (VAE) model to compress thousands of genes into latent vectors in a low-dimensional space. We then demonstrate that these encoded vectors could accurately impute drug response, outperform standard signature-gene based approaches, and appropriately control the overfitting problem. We apply rigorous quality assessment and validation, including assessing the impact of cell line lineage, cross-validation, cross-panel evaluation, and application in independent clinical data sets, to warrant the accuracy of the imputed drug response in both cell lines and cancer samples. Specifically, the expression-regulated component (EReX) of the observed drug response achieves high correlation across panels. Using the well-trained models, we impute drug response of The Cancer Genome Atlas data and investigate the features and signatures associated with the imputed drug response, including cell line origins, somatic mutations and tumor mutation burdens, tumor microenvironment, and confounding factors. In summary, our deep learning method and the results are useful for the study of signatures and markers of drug response.
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BACKGROUND: Systemic anticancer therapies can produce acute and chronic organ damage, but the eye is usually considered a protected site. Nonetheless, the oculo-visual system has a potentially high degree of sensitivity to toxic substances. Ocular toxicity induced by cancer chemotherapy includes a broad spectrum of disorders, reflecting the unique anatomic, physiologic, and biochemical features of this essential organ. METHODS: A review of the literature regarding the ocular toxicity of chemotherapeutic agents, hormonal agents, biologic agents, and high dose chemotherapy with allogeneic and autologous bone marrow transplantation was conducted. RESULTS: Ocular toxicity induced by anticancer chemotherapy is not uncommon. The development of more aggressive regimens as well as new agents and combination chemotherapies have resulted in a significant increase of reported cases of chemotherapy-induced ocular side effects. In most instances, the mechanisms of ocular toxicity continue to be poorly understood. CONCLUSIONS: Ocular toxicities induced by chemotherapeutic agents are generally not preventable; therefore, clinicians must be aware of potential vision-threatening complications. Prompt consultation with an ophthalmologist can lead to early detection, proper diagnosis, and appropriate therapeutic measures. Dose reduction or discontinuation of incriminated drugs may help in reducing the severity and the duration of side effects.