Major milestones in translational oncology

Abstract

Translational oncology represents a bridge between basic research and clinical practice in cancer medicine. Today, translational research in oncology benefits from an abundance of knowledge resulting from genome-scale studies regarding the molecular pathways involved in tumorigenesis. In this Forum article, we highlight the state of the art of translational oncology in five major cancer types. We illustrate the use of molecular profiling to subtype colorectal cancer for both diagnosis and treatment, and summarize the results of a nationwide screening program for ovarian cancer based on detection of a tumor biomarker in serum. Additionally, we discuss how circulating tumor DNA can be assayed to safely monitor breast cancer over the course of treatment, and report on how therapy with immune checkpoint inhibitors is proving effective in advanced lung cancer. Finally, we summarize efforts to use molecular profiling of prostate cancer biopsy specimens to support treatment decisions. Despite encouraging early successes, we cannot disregard the complex genetics of individual susceptibility to cancer nor the enormous complexity of the somatic changes observed in tumors, which urge particular attention to the development of personalized therapies.

Keywords: Biomarkers; Breast; Cancer vaccines; Colorectal; Early diagnosis; Genetic profile; Immunotherapy; Individual risk; Liquid biopsy; Lung; Mutational landscape; Next generation sequencing; Ovarian; Prostate; Tumorigenesis.

Fig. 1

Tommaso A. Dragani. Tommaso A. Dragani is Director of the Research Unit of Genetic Epidemiology and Pharmacogenomics at Fondazione IRCCS Istituto Nazionale dei Tumori in Italy. He has been a pioneer of research on the genetic predisposition to cancer. His early studies in animal models led to the identification and characterization of chromosomal loci that determine the inherited predispositions to liver, lung and skin tumorigenesis. He has since extended this research to humans by carrying out population-based case-control studies to identify genetic polymorphisms associated with the risk for and prognosis of lung cancer, thus contributing to the field of complex (polygenic) genetic predisposition to cancer. Dr. Dragani’s research group discovered the mechanism underlying the association between polymorphisms in nicotinic receptor subunit genes and the risks of both lung cancer and nicotine dependence. Additionally, he led the first genome-wide pharmacogenomic study on pain relief, which discovered that multiple loci modulate the response to opioid therapy for cancer pain

Fig. 2

Antoni Castells. Antoni Castells is Associate Professor at the University of Barcelona, School of Medicine. He is a specialist in gastroenterology, and since 2016, has been Medical Director of the Hospital Clinic of Barcelona. His professional activity has been related to colorectal cancer, involving its diagnosis, therapeutics and prevention, being Coordinator of the Colorectal Cancer Unit and Co-coordinator of the Barcelona Colorectal Cancer Screening Program. His research achievements are mainly derived from two internationally-recognized studies, the EPICOLON and COLONPREV projects, in which he is leading principal investigator

Fig. 3

Vathany Kulasingam. Vathany Kulasingam completed her PhD at the Department of Laboratory Medicine and Pathobiology, University of Toronto. Following her PhD, she completed a post-doctoral training diploma program in Clinical Chemistry at the University of Toronto. Dr. Kulasingam is currently a clinical biochemist at the University Health Network in Toronto, an Assistant Professor at the Faculty of Medicine, University of Toronto, and a Fellow of the Canadian Academy of Clinical Biochemistry. Her current interests include novel tumor biomarker discovery and application of proteomics to clinical practice

Fig. 4

Eleftherios P. Diamandis. Eleftherios P. Diamandis is currently Professor and Head, Division of Clinical Biochemistry, Department of Laboratory Medicine and Pathobiology, University of Toronto, Biochemist-in-Chief at University Health Network, and Division Head of Clinical Biochemistry at Mount Sinai Hospital, Toronto. He is also a “Hold’em for Life” Chair on Prostate Cancer Biomarkers, a Corresponding Member of the Academy of Athens, a Member of the Royal Society of Canada and the Canadian Academy of Health Sciences, and an elected Fellow of the American Association for the Advancement of Science

Fig. 5

Helena Earl. Helena Earl is an academic clinician in Medical Oncology and currently Professor of Clinical Cancer Medicine at the University of Cambridge, Department of Oncology and a Principal Investigator of the NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre. She is co-lead for the Breast Cancer Programme at the Cancer Research UK Cambridge Cancer Centre and significantly contributes to the translational endeavor in precision medicine and the development of personalized treatment pathways in breast cancer. In Cambridge, she is the cancer lead in the collaborative workstream for novel adaptive trial designs

Fig. 6

Wade Iams. Wade Iams has recently completed his Chief Residency at Vanderbilt University Medical Center, and is beginning his clinical fellowship in hematology/oncology at McGaw Medical Center of Northwestern University. He is an active member of the American Society of Clinical Oncology (ASCO), International Association of Lung Cancer Research (IASLC), and the American Association for Cancer Research (AACR), where he also serves on the Associate Member Fundraising Committee. He has been awarded a Young Investigator Award from Adaptive Biotechnologies as well as travel awards from the AACR and IASLC for early-career research on thoracic malignancies

Fig. 7

Christine M. Lovly. Christine M. Lovly is an Assistant Professor of Medicine and Cancer Biology at Vanderbilt University Medical Center. Dr. Lovly is a physician-scientist with a special interest in thoracic malignancies. Her laboratory research is directed at understanding and developing improved therapeutic strategies for specific clinically relevant molecular subsets of lung cancer. Dr. Lovly has received independent grant funding from several foundations, including Uniting Against Lung Cancer, Conquer Cancer Foundation, LUNGevity, Damon Runyon Foundation, and V Foundation. She is an active member of the American Society of Clinical Oncology (ASCO), the International Association for the Study of Lung Cancer (IASLC), and the American Association for Cancer Research (AACR). She is also co-editor-in-chief for the website www.mycancergenome.org, a Vanderbilt initiated, freely available website which aims to provide health care practitioners, patients and advocates with up-to-date information regarding genetically informed cancer medicine

Fig. 8

Advances in the treatment of patients with lung cancer over the past 50 years. Advances in the treatment of patients with lung cancer over the past 50 years can be divided into cytotoxic chemotherapy, oncogene-targeted therapy and immunotherapy, with the most recent advances being in oncogene-targeted therapy and immunotherapy. All FDA approvals noted apply to patients with locally advanced or metastatic lung cancer

Fig. 9

J.P. Michiel Sedelaar. J.P. Michiel Sedelaar is the deputy-chief of the department of Urology at Radboud University Medical Center, Nijmegen, the Netherlands. He finished his urology training in 2007 and in 2008–2009 he was a post-doc researcher at the Johns Hopkins Medical Institutes in Baltimore, MD, USA. His focus during that time was the development of smart-drugs for detection and treatment of prostate cancer and steroidogenesis of prostate cancer. Since 2010, he returned to Nijmegen for an onco-urology staff position. His research achievements are mainly on imaging studies for prostate cancer (use of MRI, MRI-guided treatments) and basic research on the androgen receptor in prostate cancer. He has national and international board functions; among others, he is the chair of the EAU-Young Urology Office

Fig. 10

Jack A. Schalken. Jack A. Schalken trained as biochemist at Radboud University Medical Center, Nijmegen, the Netherlands, where he is Director of the urology research lab. His work focusses on translational research, with an emphasis on biomarkers and novel therapeutic targets such as epithelial–mesenchymal transition. His team’s research led to the clinical introduction of the first urine-based prostate cancer test (Progensa PCA3, 2006) and more recently to the SelectMdX test, which has been commercially available for clinical use since 2015. In 1996, he was appointed as full professor at the University of Utrecht (experimental oncology), and in 2001 as professor of experimental urology (Radboud University Medical Center). He has been awarded several scientific awards, most recently the Dominique Chopin award (2015) for his long-term contribution to the field