Methods for analysis of the cancer microenvironment and their potential for disease prediction, monitoring and personalized treatments

Progression from a normal cell to a cancer cell usually requires several genetic alterations including overexpression or alterations of oncogenes and loss of tumor suppressor genes [1]. Whole genome sequencing studies reveal that hundreds of genes are more or less frequently mutated in cancer [2]. Most mutated genes are only altered in a small subset of patients with a particular cancer disease, while only a few genes are commonly mutated. However, collectively rare mutations make up a large proportion of the mutational landscape of cancer. While the DNA sequence acts as a blueprint in the molecular assembly of an individual, the functionally active components of a cell are RNA and proteins. Analysis of RNA and protein are therefore needed to determine to what extent the genetic information is utilized to promote growth and survival of cancer cells. However, the question is whether genetic alterations propagating into expressed RNA and proteins are the sole factor causing and sustaining cancer, and how much this is influenced by epigenetic alterations [3], or if there are additional external factors. To what extent do cells determine their own fates?For all multicellular organisms intercellular communication is essential to ensure proper organization of individual cells in tissues and organs. The signals transferred between cells provide information that determines the fate of the recipient cells, regulating growth, survival and differentiation. In order to decide to which signals they should respond, cells express different panels of receptors that subsequently will relay the signals, via intricate networks of protein-protein interactions where the activity status of the individual proteins are regulated by post-translational modifications (PTMs). The observed genetic and epigenetic alterations in cancer cells act to promote sustained growth and survival and to overcome the growth restraints from the surrounding cells. The extent of the interplay between cell types