Remodelling of the tumour microenvironment by the kallikrein-related peptidases

Kallikrein-related peptidases (KLKs) are critical regulators of the tumour microenvironment. KLKs are proteolytic enzymes regulating multiple functions of bioactive molecules including hormones and growth factors, membrane receptors and the extracellular matrix architecture involved in cancer progression and metastasis. Perturbations of the proteolytic cascade generated by these peptidases, and their downstream signalling actions, underlie tumour emergence or blockade of tumour growth. Recent studies have also revealed their role in tumour immune suppression and resistance to cancer therapy. Here, we present an overview of the complex biology of the KLK family and its context-dependent nature in cancer, and discuss the different therapeutic strategies available to potentially target these proteases. This Review discusses the complex biology of the family of kallikrein-related peptidases and their context-dependent functions in cancer and the tumour microenvironment, as well as their role in tumour immune suppression and resistance to cancer therapy.