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Translational research in oncology—10 years of progress and future prospects

Key Points

  • The landscape of translational oncology has shifted dramatically over the past 10 years, characterized by the introduction of ever-more-sophisticated molecular tools into the clinic

  • Translational cancer-biology studies have markedly improved preclinical models applicable for therapeutics development, as well as our understanding of the roles of inflammation and altered intermediary metabolism in carcinogenesis

  • Translational cancer diagnostics and therapeutics have been revolutionized by the molecular characterization of human tumours, a process that now underlies the development of molecularly-targeted, rather than broadly cytotoxic, anticancer therapies

  • Improvements in molecular tumour-classification techniques will permit their widespread application for patients at diagnosis, disease recurrence, and during therapy, supporting continuous adaptation of therapeutic approaches to evolving tumour characteristics

Abstract

International efforts to sequence the genomes of various human cancers have been broadly deployed in drug discovery programmes. Diagnostic tests that predict the value of the molecularly targeted anticancer agents used in such programmes are conceived and validated in parallel with new small-molecule treatments and immunotherapies. This approach has been aided by better preclinical cancer models; an enhanced appreciation of the complex interactions that exist between tumour cells and their microenvironment; the elucidation of interactions between many of the genetic drivers of cancer, including oncogenes and tumour suppressors; and recent insights into the genetic heterogeneity of human tumours made possible by extraordinary improvements in DNA-sequencing techniques. These advances are being employed in the first generation of genomic clinical trials that will examine the feasibility of matching a broad range of systemic therapies to specific molecular tumour characteristics. More-extensive molecular characterization of tumours and their supporting matrices are anticipated to become standard aspects of oncological practice, permitting continuous molecular re-evaluations of human malignancies on a patient-by-patient and treatment-by-treatment basis. We review selected developments in translational cancer biology, diagnostics, and therapeutics that have occurred over the past decade and offer our thoughts on future prospects for the next few years.

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Figure 1: Timeline of 10-year translational research for oncology and prospects for the future.
Figure 2: Improving tumour models for cancer biology and drug development.
Figure 3: Human tumour tissue-based experimental therapeutics for cancer.
Figure 4: Multiple biomarkers of DNA damage imaged simultaneously in tumour biopsies following systemic cancer therapy.
Figure 5: Clinical demonstration of ER in metastatic breast cancer and blockade of receptor occupancy by endoxifen.

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Acknowledgements

This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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Doroshow, J., Kummar, S. Translational research in oncology—10 years of progress and future prospects. Nat Rev Clin Oncol 11, 649–662 (2014). https://doi.org/10.1038/nrclinonc.2014.158

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