Chemical Biology as a Driver of Innovation in Cancer Research and Drug Discovery

Abstract

Several months ago, as we were launching the Cell Chemical Biology Call, we took some time to explain why we believe that chemical biology epitomizes what a multidisciplinary scientific field is all about (http://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(17)30104-6). It is a discipline that successfully operates within the chemistry-biology-medicine continuum, thanks to its multidisciplinary nature and the mindset that its members have.Cancer research is one of those areas where chemical biology efforts have made remarkable and real scientific and clinical contributions. Efforts in chemical biology laboratories have produced a range of small molecules that are making a difference in the clinic today. Probably the most prominent example of such a compound is imatinib, which targets the active sites of a number of tyrosine kinases, including—most importantly—Bcr-abl kinase, and whose success solidified the importance of targeting oncogene addiction in cancer drug discovery anticancer drugs.In addition to clinically important small molecules, chemical biology efforts have led to the development of a large number of chemical probes that are currently in widespread use in basic cancer biology, like JQ1, a selective inhibitor of the BET family of bromodomains, which was disclosed in 2010 (http://www.nature.com/nature/journal/v468/n7327/full/nature09504.html) and appears in close to 350 research articles based on a recent Scopus keyword search. The use of chemical probes in cancer biology has been so widely successful that chemical biologists recognize the need to educate those who use the tool compounds on both the benefits and potential pitfalls (http://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30303-3).Given all this, we decided that the second special issue under the name Cell Chemical Biology should focus on cancer research and how chemical biology is pushing the boundaries of fundamental biology, technology, and clinical science.In general, the use of chemical biology in drug discovery has come of age, with a growing number of systems-level (omic) and cellular technologies in place to identify potential targets; phenotypic, targeted, and computational screens to identify compounds that impinge on disease states; and sophisticated methods to link compound activities and targets. Nowhere is the impact clearer than in cancer—an umbrella term for a myriad of disease states that all boil down to derangements in cellular pathways—where chemical biology offers technologies and molecules to develop precision medicine.For this special issue, we picked nine topics to elaborate on two main broad themes, one that revolves around the idea of chemical biology as a driver of technology development and the other that showcases how chemical biology is helping better understand basic cancer biology, leading to drugs.For the more technological aspects of chemical biology in the context of cancer research, we highlight the value of bridging medicinal chemistry and chemical biology efforts, as discussed by Plowright et al.; the discovery of new biomarkers using high-throughout screens as described by Williams et al.; and tumor organoids, including patient-derived cells, as drug screening platforms, the focus of the review by Weeber et al.We transition the discussion from more technological to more basic science questions via a piece by Sharifnia et al. that focuses on rare cancers, as these represent a major area where technology and basic biology overlap to a great extent. We continue the special issue with a review by Hengel et al. highlighting the impact of chemical biology on the area of DNA repair research in the context of cancer and a piece by Ribich et al. discussing how chemical biology has been enabling cancer epigenetics research. Finally, we round up the special issue with three reviews that bring us closer to the clinical practice, with description of small molecule targets in immune-oncology by Dhanak et al., small molecule targets in cancer metabolism by Luengo et al., and targeted protein degradation as anticancer drug strategy by Cromm et al.Cancer research is vast, varied, and broad, as is the disease itself. This also means that the number of entry points and the impact chemical biology can have on cancer research are huge. We expect that, in the years to come, we will continue to see a growing interest among cancer biologists and clinicians in chemical biology and the other way around. As a journal, Cell Chemical Biology remains strongly interested in studies, reviews, and perspective in this area. We invite you to enjoy this special issue and to send us your innovative, provocative, and exciting cancer chemical biology stories. Our broad hope is that through multidisciplinary efforts like those highlighted in our special issue, we will be able to move the needle on cancer detection, diagnosis, and treatment.