Introduction

Cancer is, first of all, the Latin word for “crab”. The oldest mentions of cancer date back to the 7th Century BC, with the first descriptions of the priests of Aesculapius (or Asclepios), the Greek-Roman god of medicine, referring to abnormal lumps that cannot disappear on their own. With the name carcinoma, the Greek Hippocrates clarified by insisting on the ability of the cancer to spread continuously until the death of the patient, before the Roman Galien introduced the term tumor in the 2nd Century AD.

Today, cancer is often associated with numbers that must be carefully disseminated and interpreted. For France in 2018, INCa estimated the number of new cancer cases at 382,000 (274 per 100,000 women, 330 per 100,000 men, median ages 67 and 68 respectively) and the number of cancer deaths at 157,400 (72.2 per 100,000 women, 123.8 per 100,000 men, median ages 77 and 73 respectively) [INS 19]. All these figures, which are steadily increasing, make cancer the leading cause of death in France ahead of cardiovascular diseases.

The number of people living in metropolitan France in 2017 who were diagnosed with cancer during their lifetime was 3.8 million, for a population of 67 million inhabitants.

The World Health Organization reported for 2018: 18.1 million new cases of cancer worldwide and 9.6 million deaths from cancer. The forecasts for 2030 are 22 and 13 million respectively [ORG 18].

These developments, however worrying they may be, can be explained first of all by two reasons independent of oncology. The world population has increased considerably. From 1950 to 1980, it grew from 2.5 to 4.5 billion people. During this period, this increase was 70 million in the United States and 12 million in France. These increases are obviously correlated with the number of cancers today. When looking at the forecast number of cancer cases we should recall that the world population grew by 5 billion between 1950 and 2015.

Then, populations have aged and continue to age: from 1950 to 2015, the increase in life expectancy was more than 20 years, more than 27 years in developing countries and more than 13 years in rich countries. With the exception of the African region, life expectancy now ranges from 70 to 80 years, depending on the country.

Moreover, while progress can be noted here and there in prevention and early detection, in several countries around the world, there is also a deterioration in lifestyles and the environment that is beginning to provoke reflection and reactions, at least in rich or rapidly developing countries.

To have a realistic view of therapeutic progress in oncology, it is necessary to look at the incidence figures, i.e. the number of new cases of cancer reported annually per 100,000 inhabitants. In the United States, for the period 2011–2015, the NIH/NCI (National Institutes of Health/National Cancer Institute) reported an average of 439 cases with a mortality rate of 196.8 for men and 139.6 for women. These numbers are increasing, but mortality rates have declined significantly over the past 25–30 years, both in the United States and France, by about minus 1% per year. Moreover, these annual mortality rates have declined faster in recent years by, for the United States, minus 1.8% for men and minus 1.4% for women over 2005–2015, and, for France, minus 2% for men and minus 0.7% for women over 2010–2018, which could result in decreases of around 35% between 2005 and 2025 [NAT 18].

After this quantified inventory, we need to briefly examine the cancer development process. In the beginning, there is the cell, from the ancient Greek kutos which gave many terms with the prefix of cyto: cytology, cytoplasm, cytotoxic.

In humans, there are more than 200 types of cells. The number of cells constituting an adult human body is estimated at a few tens of trillions. A large part of these cells, 75%, are red blood cells and platelets found in the blood. Without nuclei, they do not divide. Other cells, including hematopoietic stem cells that are the source of all blood cells, can divide and generate new cells that replace the aging or dead cells (apoptosis) that the body gets rid of every day1.

To date, cancers (nearly 100 today) are mainly named after the organ or tissue they affect. The most frequently diagnosed cancers are breast, prostate, lung, colorectal, liver, bladder, skin (melanoma) and brain cancers. In hematological cancers (leukemias, lymphomas, myelomas), cells proliferate in the blood or invade hematopoietic tissues (bone marrow) or lymphoid organs (thymus, spleen, lymph nodes). Cancers are also classified by the type of original cells2. Then, they are referred to as carcinoma, sarcoma, lymphoma, glioma, etc.

The onset of cancer is the result of a series of complex molecular events that are beginning to be well understood. Six biological modifications can be defined that contribute to the transformation of a cell into a cancerous cell:

• – ability to divide;
• – escape from growth suppressors;
• – resistance to cell death;
• – replicative immortality;
• – induction of angiogenesis;
• – activation of invasion factors [HAN 11].

With the recent progress of research at the molecular level and with the current possibilities of genome sequencing, it is possible to observe genetic anomalies and changes in the expression of the genes responsible for the biological modifications. These genetic anomalies and mutations may be due to failure to repair the many natural genetic events and also to the way of life influenced by smoking, alcohol, bad UV exposure or exposure to carcinogens. These mutations mainly concern proto-oncogenes which positively control cell divisions but which can become oncogenic (cancer cell producers). Cell division is indeed a complex process, finely tuned by a small part of the 25,000 genes found in each cell. When this control is lost, the cell acquires the ability to divide indefinitely. These mutations also concern tumor suppressor genes, which inhibit cell proliferation, genes dedicated to DNA repair, which prevent mutations from accumulating, and genes that control the so-called programmed cell death or apoptosis.

Apoptosis is a mechanism in genes that eliminate cells that the body must get rid of, especially damaged cells. When this process is disrupted, cells continue to proliferate and accumulate to form malignant tumors called cancers. Finally, for cancer cells to invade surrounding tissues and eventually spread into metastases by leaving their original location through the blood or lymphatic networks, they must trick and block the immune system. This is the dreaded metastatic process.

The interest of genomics, immunology, cytological and histological analyses and multiple radiological imaging is becoming obvious. These analyses produce massive databases, and artificial intelligence (AI) must be used to take advantage of data from the patient and his or her type of cancer and to propose personalized treatments.

The diagnosis and treatment of cancer has undergone a major evolution in recent years, with several innovations that seem useful to elucidate and explain, particularly in the context of a new personalized and participatory medicine that should greatly involve the patient. This is especially so since these developments, driven by the now proliferating research, computing power and AI, could lead more or less quickly to a therapeutic revolution in cancer therapy.

Here is a brief overview of the six chapters of this book.

Chapter 1: Genomics and Epigenetics

Let us briefly recall some elements of genetics. In the human body, all cells capable of division contain 23 pairs of chromosomes that carry about 25,000 genes and constitute the individual’s genome. The chromosomes and therefore the genes are constituted by deoxyribonucleic acid (DNA) that contains pairs of nucleotides characterized by nitrogenous base pairs – adenine and thymine (A, T), guanine and cytosine (G, C) – arranged in two complementary strands wound in the shape of a helix.

The transcription of genes into messenger RNA (transcripts or transcriptome) then allows, through the genetic code, their translation into distinct proteins essential for the functioning of body cells. There can be several transcripts for the same gene, hence the existence of about one hundred thousand different proteins in the human body (the proteome).

When examining an individual genome, genetic abnormalities can be found: either they are widespread and inherited and they may cause genetic diseases or they concern only certain cells and they may cause cancer. In the latter case, the mutations are acquired and not transmissible or inherited. In this respect, cancer is also a genetic but so-called somatic disease.

Chapter 2: Overview of Cancer Chemotherapy

For 60 years, chemotherapy has been the first medication to treat cancer by killing cancer cells. A large number of cytotoxic products, synthetic or natural, have been developed and marketed after screening in in vitro studies, preclinical studies in laboratory animals, most often mice transplanted with tumor cells, and in several stages of clinical trials involving cancer patients. Besides proven efficacy, the main difficulty lies in the low specificity of the drugs, which affect all cells, particularly the normal cells that divide the most: the bone marrow cells that produce blood cells. Additionally, chemoresistance appears during treatment. Moreover, the patient often suffers from more...