Cancer 2021: New therapeutic approaches for the treatment of cancer — building on advances in cancer biology and the molecular genetics of cancer
Introduction
The past decade has been revolutionary in our understanding of the molecular pathology of cancer, underscored by advances in genomics technology facilitating the routine DNA and RNA sequencing of tumors, single-cell transcriptomic profiling of cancer cells, advances in understanding the epigenetics of cancer, and functional genomics and whole-genome clustered regularly interspaced short palindromic repeats (CRISPR) screens contributing to the functional characterization of genetic drivers of tumor growth and progression. These advances have had a direct translational impact on the growing success of oncology precision medicine-targeted therapies directed against tumors and components of the tumor microenvironment [1,2] and in a virtual explosion of novel cellular and checkpoint immunotherapies [2, 3, 4] for the treatment of various solid and hematological malignancies. In the last decade alone, Food and Drug Administration approval of new cancer drugs accounted for more than 25% of all new drug approvals [5], a paradigm shift from trends in the early1980s at the onset of the revolution in genomic technologies.
In this special issue, a series of articles prepared by leaders in their respective fields describe compelling and effective new therapeutic approaches to treat cancers building on the extraordinary advances made in cancer biology and molecular genetics particularly in the last decade and are focused on three distinct therapeutic approaches. These approaches include targeting previously ‘undruggable’ but critically important oncology targets via proximity-inducing small-molecule strategies leading to selective target protein degradation (proteolysis targeting chimera (PROTAC) approaches); breakthrough adaptive cellular immunotherapies for hematological and some solid tumors (novel chimeric antigen receptor (CAR)-T approaches); and modulating essential epigenetic mechanisms critical in tumor growth and resistance via modulating the fidelity of RNA splicing processes and polyadenylation.
Section snippets
Special topics on new therapeutic approaches for cancer
A rapidly evolving area in the oncology therapeutic arena is the identification and development of bifunctional, proximity-inducing small molecules connecting a ligand binding to a protein of therapeutic interest linked to an E3 ubiquitin ligase — recruiting ligand that mediates degradation of proteins of interest through the ubiquitin-proteasome system (PROTAC approaches; [6,7]). Among the most widely used moieties are low nanomolar binding ligands for Von Hipel Lindau (VHL) and cereblon,
Conflict of interest statement
Nothing declared.
Bruce Ruggeri, PhD is currently the Vice President and Head of Biology at Prelude Therapeutics Inc., since mid-2019, and was previously the Chief Scientific Officer at Champions Oncology Inc. He received his PhD in Biochemistry at the University of Pennsylvania and completed post-doctoral studies in experimental and molecular pathology at the Fox Chase Cancer Center in Philadelphia. He has worked in basic and applied oncology and cancer biology research for almost 30 years throughout his career
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Cited by (0)
Bruce Ruggeri, PhD is currently the Vice President and Head of Biology at Prelude Therapeutics Inc., since mid-2019, and was previously the Chief Scientific Officer at Champions Oncology Inc. He received his PhD in Biochemistry at the University of Pennsylvania and completed post-doctoral studies in experimental and molecular pathology at the Fox Chase Cancer Center in Philadelphia. He has worked in basic and applied oncology and cancer biology research for almost 30 years throughout his career in academia and the pharmaceutical industry. He held an academic teaching and research appointment for 5 years as an Associate Professor at Hahnemann University in Philadelphia before joining the pharmaceutical industry in 1997. Throughout his 25-year biotech and biopharma industry career, he has worked in target-directed small molecule oncology drug discovery and translational pharmacology through early clinical development across numerous drug discovery programs spanning a multitude of therapeutically relevant molecular targets, mechanisms, and signaling pathways.