Computational Characterization of Membrane Proteins as Anticancer Targets: Current Challenges and Opportunities

International Journal of Molecular Sciences, vol. 25, pp. 3698

Abstract

Cancer remains a leading cause of mortality worldwide and calls for novel therapeutic targets. Membrane proteins are key players in various cancer types but present unique challenges compared to soluble proteins. The advent of computational drug discovery tools offers a promising approach to address these challenges, allowing for the prioritization of "wet-lab" experiments. In this review, we explore the applications of computational approaches in membrane protein oncological characterization, particularly focusing on three prominent membrane protein families: receptor tyrosine kinases (RTKs), G protein-coupled receptors (GPCRs), and solute carrier proteins (SLCs). We chose these families due to their varying levels of understanding and research data availability, which leads to distinct challenges and opportunities for computational analysis. We discuss the utilization of multi-omics data, machine learning, and structure-based methods to investigate aberrant protein functionalities associated with cancer progression within each family. Moreover, we highlight the importance of considering the broader cellular context and, in particular, cross-talk between proteins. Despite existing challenges, computational tools hold promise in dissecting membrane protein dysregulation in cancer. With advancing computational capabilities and data resources, these tools are poised to play a pivotal role in identifying and prioritizing membrane proteins as personalized anticancer targets.

Authors 5

1. Marina Gorostiola González Aachen Leiden Academic Centre of Drug Research

   Leiden University · Oncode Institute

   Affiliation as printed

   Leiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

   Oncode Institute, 2333 CC Leiden, The Netherlands

2. Willem Jespers Aachen Leiden Academic Centre of Drug Research

   Leiden University

   Affiliation as printed

   Leiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

3. Adriaan P. IJzerman Aachen Leiden Academic Centre of Drug Research

   Leiden University

   Affiliation as printed

   Leiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

4. Laura H. Heitman Aachen Leiden Academic Centre of Drug Research

   Leiden University · Oncode Institute

   Affiliation as printed

   Leiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands

   Oncode Institute, 2333 CC Leiden, The Netherlands

5. Gerard J. P. van Westen corresponding Aachen Leiden Academic Centre of Drug Research

   Leiden University

   Affiliation as printed

   Leiden Academic Centre of Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands