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Webber et al prostate cancer microenvironment

also. Researchers require better models that more review by Falconer and Loadman . Furthermore, the
[5]
accurately represent the tumour microenvironment, but authors consider MT-MMP expression and proteolytic
this requires collaboration between basic scientists and capacity in the design of potential new therapies
clinicians. Only by working together can we truly hope against metastatic prostate cancer.
to develop personalised, effective, cancer therapies
and therefore improve the survival of men with prostate Cell to cell communication plays a key role in the
cancer. The two commentaries by Mason and development of prostate cancers. As is evident from
[1]
Maitland encapsulate seven in-depth reviews, which numerous articles within this special issue, such
[2]
are focussed on key aspects that contribute to prostate communication occurs not only between cancer
cancer aggressiveness. cells but also between all cells within the tumour
microenvironment, resulting in changes to the
Perhaps one of the most studied aspects of prostate local environment that favour tumour growth and
cancer is the role of androgens. The prostate metastasis. Historically, many studies have focussed
requires androgens, a family of hormones including on soluble growth factors and cytokines, but there is
testosterone, which interact with the androgen emerging evidence highlighting the role of extracellular
receptor (AR) to regulate normal physiological vesicles. Such vesicles can be divided into two
function. Aberrant androgen signalling, however, can broad sub-categories, microvesicles and exosomes.
drive the formation and growth of prostatic tumours. Whilst there have been many studies exploring the
Androgen deprivation therapy therefore remains a role of extracellular vesicles in cancer, relatively few
pivotal treatment for prostate cancer. Abiraterone and of these studies have focussed on prostate cancer.
enzalutamide are two such therapeutic agents used Shephard et al. review the reported functions of
[6]
to treat prostate cancer. Regrettably, tumours can extracellular vesicles from diverse malignancies to
become resistant to such therapies, and there is urgent identify those with potential relevance to prostate
need for new therapies to improve patient survival. cancer. It is clear that extracellular vesicles represent
Pippione et al. review the androgen-AR axis and a means of delivering a complex assortment of factors
[3]
the potential targeting of steroidogenic enzymes as a from one cell to another, actively contributing to the
means of overcoming resistance to existing prostate disease progress. Such vesicles also represent an
cancer treatments. attractive source of biomarkers for both diagnostic
and prognostic purposes.
Cancer progression is associated with a dysregulated
balance between cellular growth, division, and cell Despite the wealth of knowledge on prostate cancer
death. Such processes are regulated by transcription and potential therapeutic interventions there remain
factors that work alone, or in combination with other many unanswered questions and challenges to
proteins, to regulate genetic expression. One family address. One such area is that of tumour heterogeneity.
of transcription factors, the HOX proteins, have been Heterogeneity within prostatic tumours is a complex
shown to contribute to interactions between prostate topic and forms the basis of an original research article
tumours and the surrounding microenvironment. by Frame et al. . When we think of heterogeneity we
[7]
Morgan and Pandha review the numerous roles of should not only consider patient variability, but also
[4]
HOX proteins in prostate cancer, ranging from regulation differences between individual tumours and sub-
of androgen-receptor sensitivity to angiogenesis and populations of cells within a tumour. Not only do the
tumour metastasis. authors consider how to tackle tumour heterogeneity,
but they introduce a new model for assessing drug
Tumour growth within the prostate, and other sites, response that takes into account this heterogeneity. As
requires remodelling of the surrounding environment. an extension of tumour heterogeneity, McKenna et al.
[8]
Matrix metalloproteinases (MMPs), a family of discusses how the presence of hypoxia, which is well-
proteolytic enzymes, have long been associated known to contribute to cancer aggressiveness and
with regulation of the extracellular matrix and tissue resistance to chemo- and radiotherapy, can be turned
remodelling. They have also been implicated in the into an opportunity for rationalised drug discovery and
initiation, progression and metastasis of multiple combination therapy while Ibrahim et al. discusses
[9]
cancer types, including prostate cancer. The MMP how tumour-initiating cells with high expression of
family is composed of two broad sub-groups, the aldehyde dehydrogenase contribute to treatment
soluble or secreted MMPs and the membrane-type resistance and tumour recurrence.
MMPs (MT-MMPs). Whilst many studies have focussed
on the soluble MMPs, the expression and roles of We would like to thank all of the contributing authors
MT-MMPs remain less clear and form the subject of for their hard work in producing the enclosed articles.

2 Journal of Cancer Metastasis and Treatment ¦ Volume 4 ¦ Aug 21, 2018