Dear Colleagues,

Cancer must be considered a genetic disease and the accumulation of molecular alterations in the genome of somatic cells is a prerequisite for cancer progression. New discoveries and insights are transforming the field of oncology at multiple levels, and at an increasing speed. For instance, the genomic maps are redesigning the tumour taxonomy by moving it from a histological to a molecular-based level. Tumour genotyping is thus increasingly assisting clinicians to individualize treatments by matching patients with the best treatment for their tumours. Furthermore, the success of cancer drugs designed to target the molecular alterations underlying tumorigenesis has proven that somatic genetic alterations are valid targets for therapy. In this issue, we will focus on central aspects of clinical tumour progression as well as relating the tumour to its global environment of the organism by addressing essential molecular aspects of cancer development.

For the cancer cells to migrate, they are dependent on their inherent cell-autonomous properties, as well as their microenvironment and the mesenchymal cells surrounding them. Thus, assemblies of diverse cell types associated with and surrounding malignant lesions are increasingly documented to be functionally important for the manifestation of symptomatic disease.

Some pleiotropic acting transcriptional factors are causally important for programming invasion, while others have been found to elicit metastasis, possibly by facilitating the spread of tumour cells by establishing mesenchymal-like traits of the original epithelial cells, so-called epithelial-to-mesenchymal transition (EMT).

Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) can now, in detail and by novel molecular techniques, be demonstrated in the blood stream and may serve as so-called liquid biopsy, becoming a new and increasingly important field of translational and clinical research. CTCs and ctDNA may provide data regarding the presence of minimal residual disease after surgery or after completion of adjuvant treatment and thus identify patients with high risk of relapse. Moreover, CTCs and ctDNA may be used to monitor the effect of ongoing systemic treatment, to reveal resistance to treatment, or even to detect relapse early.

Through the technical development of new biochemical tools such as metabolomics, studies of cancer cell metabolism have extended our knowledge of the mechanisms and role of the metabolic reprogramming in cancer for tumor growth, metastasis, and drug resistance.

This SI will also address the advent of novel immunomodulatory strategies targeting immune checkpoints, thus meaning that the field of systemic cancer therapy for metastatic disease has entered an exciting new era. Indeed, the time of personalised medicine has now definitely arrived, as new immunomodulatory techniques and technological innovations continue to advance the field of cancer immunotherapy. We will adress this important topic using a chemotherapy-resistant tumour, i.e. kidney cancer (or pancreatic adenocarcinoma), as an example of the progress in this new field of cancer therapeutics.

Dr. Rune Smaaland
Guest Editor

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• Tumour genotyping
• tumour taxonomy
• microenvironment
• mesenchymal cells
• EMT
• CTCs
• ctDNA
• metabolomics
• metabolic reprogramming
• biological clocks
• circadian
• chronotherapy
• bone marrow (BM)
• DNA replication
• immunomodulatory
• kidney cancer