Given the success of the previous volume,
Altered Expression of Proteins in Cancer: Function and Potential Therapeutic Targets, we are pleased to announce the launch of Volume II
Designing innovative cancer therapies requires extensive characterization of the genetic, biochemical, and cellular alterations causing tumor development and progression. Cancer hallmarks involve coordinated transcriptional programs with altered protein expression levels. These proteins are associated with metabolism, apoptosis, epigenetics, signaling pathways, tumor microenvironment, protein synthesis and degradation, and DNA structure and replication, all linked to cancer development and progression.
Reprograming of energy metabolism is a hallmark of most cancers, involving altered expression of glucose transporters, hexokinase, succinate dehydrogenase, pyruvate dehydrogenase kinase, as well as fatty acid, amino acid metabolism, and other pathways. These alterations provide cancer cells with the resources needed for continuous proliferation. Metabolic alterations in cancer also affect gene expression, enabling cellular adaptation to nutritional needs during tumor progression. Another cancer hallmark is apoptosis reprogramming, via down-regulation of pro-apoptotic, such as Bax and Bak, and up-regulation of anti-apoptotic proteins, such as B-cell lymphoma-2 (Bcl-2), Bcl-xL, apoptosis-inducing factor (AIF), second mitochondria-derived activator of caspase (SMAC) and the voltage-dependent anion channel 1 (VDAC1). Reprogramming of both metabolism and apoptosis involves up- and/or down-regulation of mitochondrial proteins and several have been identified as targets for cancer therapy. The expression of transcription factors (TFs) is also altered. The tumor-suppressor DNA repair factor P53 is usually down-regulated or silenced, while c-Myc and the hypoxia-inducible factor-1α (HIF-1α) protein are up-regulated. Their interplay determines expression levels of other TFs and genes regulating the “transformed phenotype”.
Other examples of tumor microenvironment and signaling pathway regulation in cancer include the epidermal growth factor receptor 2 (Her2) and vascular endothelial growth factor (VEGF). Her2 is up-regulated in breast and gastric/gastroesophageal cancers, for which different strategies were designed to inhibit signaling that promotes tumor growth. Inhibitors of the up-regulated VEGF decrease tumor vascularization, being effective against pancreatic, prostate and metastatic colorectal cancer, among others.
These examples uncover the significance of protein landscape alterations in cancer, controlling a continuum of cellular functions. Modulation of such protein levels is a potent therapeutic strategy, becoming more widely used in patients.
To deeply understand the role and therapeutic potential of up- or down-regulated proteins in cancer, extensive research needs to be gathered. The major goal of this Research Topic is to highlight the relevance of protein up/down-regulation in cancer, as potential therapeutic targets.
Within any cancer type, we welcome manuscripts reporting high-quality Original Research on (but not limited to):
• Presenting new proteins that are up- or down-regulated in tumors, in comparison to homologous healthy tissue.
• Uncovering the pathophysiological effects of the selected up- or down-regulated protein.
• Monitoring up- or down-regulated protein levels during cancer progression.
• Addressing subcellular localization of the up- or down-regulated protein, regarding its known and/or new function.
• Introducing specific inhibitors (small molecules, monoclonal antibodies, siRNA, peptides etc.) targeting the selected protein, as a potential therapeutic in cancer.
• Modulation of up- or down-regulated protein levels to alleviate cancer phenotypes, in cellular and/or animal models, as a prospective cancer therapy.
We also welcome comprehensive Review manuscripts on specific proteins described as up- or down-regulated in one or more cancer types. These literature reviews should highlight, besides their association with cancer, any controversies and further perspectives.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.