HPV is the world’s most common sexually transmitted infection: most of us have already acquired it by the time we become adults. While HPV is also the key source of cancer, in theory, it should pose little threat. Medical science already possesses a superior means of tracking, monitoring, and stopping this virus from becoming cervical cancer, and the body carries a natural ability to clear it. And yet, it’s society’s hang-ups about HPV – the stigma of acquiring it through sexual contact – that often get in the way of rationally addressing cervical cancer through widespread vaccination and screening. To encourage people to embrace these two highly effective means of prevention, we must dispel the mysteries of HPV and embrace its ubiquity. If we want to eliminate a cancer caused by a common viral infection, we need to take a closer look at the misguided notions associated with HPV – fears that only foster its spread – and be prepared to defuse them.

Chapter 5 reviewed the consequences at the level of protein structure and function of the vast range of mutations that can befall the human genome and contribute to cancer. The extent of this range makes it unsurprising that most aspects of normal cellular behaviour are subverted in the development of tumours. This chapter reviews these changes that essentially define a tumour cell. They include a switch to aberrant signalling in both pro- and anti-proliferative pathways, the acquisition of the capacity to avoid cell death and to replicate indefinitely, and perturbation of the normal metabolic profile. In addition, dynamic interactions between tumours and normal cells in their environment can progressively co-opt inflammatory and immune responses so that they support rather than inhibit tumour growth and can recruit host endothelium to provide a blood supply. The defining feature of malignant tumours is the ability of cells to migrate through adjacent tissue and eventually to colonise distant sites. This process of metastasis is poorly understood at the molecular level. It remains essentially untreatable and is the major cause of cancer death.

Chapter 4 introduced the concept of information transfer to cells whereby chemical signals (hormones and cytokines) transmit information across the outer, plasma membrane via protein receptors that, in turn, activate relays of proteins converging on the nucleus to direct appropriate patterns of gene expression. Prominent components of such signalling networks in the context of cancer are receptor tyrosine kinases (RTKs) that signal via RAS, a molecular switch, to the mitogen-activated protein kinase (MAPK) pathway and other protein relays that control aspects of normal cell growth. These networks show aberrant behaviour in most human tumours due to activating mutations in RAS or other components. Oncogenic RAS signalling frequently combines with abnormal activity of MYC, a central regulator of cell growth and proliferation, in tumour development.

Chapter 3 reviewed the extraordinary progress in genome sequencing from the completion of the Human Genome Project to the present when it can be said to be crucial in practically every area of biological research. In the context of cancer, huge sequence databases are under construction that have already catalogued several hundred mutations in potential cancer ‘driver’ genes, the ultimate aim being to define mutational signatures for the major cancers. The assignation of ‘potential driver’ distinguishes genes and their protein products that are known or thought to be involved in the regulation of cell proliferation from the majority of ‘passenger’ mutations (see Chapter 2). Before we turn to how mutations in specific genes might cause abnormal proliferation, it behoves us to review how, in normal cells, information from the outside world is transmitted to the cell interior and to the nucleus so that gene expression is appropriately regulated.

Chapter 2 summarised the many and varied factors that can contribute to cancer. A critical point to emerge is that the causes fall into two broad classes: those over which we have control and those we have to live with. Prominent among the former are tobacco use, excessive consumption of red and processed meats, and pollution, particularly of drinking water. It’s a striking fact that elimination of these would reduce the global cancer burden by at least three-quarters. The fact that, although cancers have multiple causes, they all appear to be driven by mutations in DNA focuses attention on the sequence of bases in DNA, and the acquisition of massive amounts of sequence data for tumours has become a cornerstone of current cancer research.

In this book, we have seen how the cancer pathway has threaded its way through human history for four millennia, its course being marked by milestones of major advances that have saved many lives and offered much hope. It is also littered with the skeletons of failed experiments and dashed optimism. In painting this contemporary picture the chapters have summarised: (1) global incidence and mortality, (2) causes, (3) DNA sequencing, (4) signalling pathways in normal cells, (5) subversion of signalling by mutations, (6) what makes a tumour, (7) major signalling pathways in tumour cells and (8) cancer detection.