The Cycle of Basic and Applied Cancer Research

Abstract

Basic molecular mechanisms take on new meaning in the context of diseases like cancer. In this cancer special issue, we want to highlight and celebrate the basic discoveries that have paved the way for the incredible progress that has been made in diagnosing and treating patients with cancer. We assume that most of our readers tend to focus on basic science, and for these readers, we hope to provide some context for the molecular mechanisms involved in the rapidly evolving cancer research field. That said, many scientists in our community are also focused on treating patients with cancer more directly, and for these readers, we aim to connect the disease biology back to the underlying mechanisms.More basic studies can inform the selection of therapeutic targets, support drug design, explain the acquisition of drug resistance, and suggest rational combination therapies (reviewed in Boshuizen et al., 1002Boshuizen et al., -1018, all ultimately improving the lives of patients with cancer, sometimes in unexpected and fortuitous ways. These basic discoveries provide the foundation upon which progress in translational and clinical research depends.Recent years have brought rapid progress in cancer research, from the sequencing of tumor genomes to the development of targeted therapies and immunotherapies. We now understand a variety of genetic and epigenetic mechanisms that drive tumorigenesis, and this knowledge has spurred breakthroughs in cancer research. Decades of basic research dedicated to understanding the function of KRAS (and oncogenes more broadly) culminated in the recent development of the first KRAS G12C inhibitors. Similarly, discoveries aimed at understanding DNA repair yielded information that led to the development of PARP inhibitors and other strategies to target the DNA damage response in cancer (reviewed in Cleary et al., 1070Cleary et al., -1085.Of course, this process works in reverse as well, as molecular biologists seek to understand the underlying biology to explain the successes and failures observed in the clinic, going back to the bench to unravel resistance mechanisms, improve therapeutic selection, and optimize drug design. In addition, drugs can make their way back to the lab as molecular tools. A notable example is the multiple myeloma drug thalidomide, also infamous for causing birth defects. The finding that thalidomide binds to and inhibits cereblon, a component of an E3 ubiquitin ligase complex, enabled development of PROTACs for targeted protein degradation.Another example of this cycle between basic and clinical work is how our understanding of transcription regulation has driven our ability to exploit this process to target cancer cells. Epigenomic dependencies in cancer have led to the development of a variety of promising compounds with therapeutic potential (reviewed in Wimalasena et al., 1086Wimalasena et al., -1095. These include inhibitors of the bromodomain and extraterminal domain-containing (BET) proteins, which have also found their way back to basic labs studying gen...

miR-499a inhibits the proliferation and apoptosis of prostate cancer via targeting UBE2V2

“…It is well known that the occurrence, development, and metastasis of different tumors are similar to a certain extent [5][6][7][8]. Cancer metastasis is an important cause of more than 90% of cancer-related deaths, but our understanding of the molecular mechanisms that regulate metastasis is still limited [9,10].…”