The role of macrophages in tumour growth and development is complex and multifaceted. Whilst there is limited evidence that tumour‐associated macrophages (TAMs) can be directly tumouricidal and stimulate the anti‐tumour activity of T cells, there is now contrasting evidence that tumour cells are able to block or evade the activity of TAMs at the tumour site. In some cases, tumour‐derived molecules even redirect TAM activities to promote tumour survival and growth. Indeed, evidence has emerged for a symbiotic relationship between tumour cells and TAMs, in which tumour cells attract TAMs and sustain their survival, with TAMs then responding to micro‐environmental factors in tumours such as hypoxia (low oxygen tension) by producing important mitogens as well as various growth factors and enzymes that stimulate tumour angiogenesis. This review presents evidence for the number and/or distribution of TAMs being linked to prognosis in different types of human malignancy. It also outlines the range of pro‐ and anti‐tumour functions performed by TAMs, and the novel therapies recently devised using TAMs to stimulate host immune responses or deliver therapeutic gene constructs to solid tumours. Copyright © 2002 John Wiley & Sons, Ltd.

Light has been employed in the treatment of disease since antiquity. Many ancient civilizations utilized phototherapy, but it was not until early last century that this form of therapy reappeared. Following the scientific discoveries by early pioneers such as Finsen, Raab and Von Tappeiner, the combination of light and drug administration led to the emergence of photochemotherapy as a therapeutic tool. The isolation of porphyrins and the subsequent discovery of their tumor-localizing properties and phototoxic effects on tumor tissue led to the development of modern photodetection (PD) and photodynamic therapy (PDT). This review traces the origins and development of PD and PDT from antiquity to the present day.

Introduction: Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. Methods: More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. Results: The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. Conclusions: With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.

Angiogenesis is the development of blood vessels from an existing vasculature. This process is fundamental to both physiological wound healing and the growth of malignant tumors, as it restores or creates a blood supply to growing tissue. In both cases, the release of angiogenic molecules by macrophages recruited to the wound or tumor site is central to the formation of these neovessels. Reduced vascular perfusion in tissues generates tissue ischemia and a marked reduction in local levels of oxygen (hypoxia) and glucose. Cells adapt by switching to anaerobic metabolic pathways, with a concomitant increase in lactate production and reduction in extracellular pH. In tumors, these microenvironmental “stress” factors stimulate tumor cells to secrete a wide array of proangiogenic cytokines and enzymes, promoting the re-establishment of a local vascular supply. Here we review the evidence that these stress factors, in particular hypoxia and high lactate levels, stimulate macrophages to perform similar proangiogenic functions in both tumors and wounds. The resolution of wounds results in restoration of tissue integrity and perfusion, and macrophage presence is reduced to preinjury levels. However, in tumors a high number of macrophages persists and might contribute to the ongoing growth, neovascularization, and metastasis of malignant cells.