The Emperor’s New Journey: ‘The Emperor of all Maladies’ has been updated

In 2010 Siddhartha Mukherjee wrote a Pulitzer Prize winning book on Cancer. It was called the Emperor of all Maladies; a title that came from the notes of a 19th century surgeon describing cancer as the “Emperor of all maladies the king of terrors.”

For too long scientists, biologists and doctors haven’t understood cancer and it has been a terrifying illness. This is changing though. In the first edition of Mukherjee’s book we learned an awful lot about the history of cancer. The research, treatment, advocacy, fund raising, prevention and drug development.

For me the big takeaways from this first book were

1. That genes cause cancer, exogenous chemicals cause cancer, and viruses cause cancer.

   
   

2. The blood brain barrier protects the spinal cord and brain from foreign chemicals and poisons. It can also keep chemotherapy out of the nervous system. This is why cancer may spread to the spine or the brain.   

3. Cancer is actually many diseases that share a fundamental feature: the abnormal growth of cells. Cancer cells exhibit six hallmarks. They acquire an autonomous drive to proliferate. They become insensitive to growth-inhibitory signals. They evade programmed cell death (apoptosis). They show limitless replicative potential. They generate their own blood supply and blood vessels. They acquire the capacity to migrate to and colonise organs and tissues throughout the body.

4. Kinases act as molecular master switches in cells. They turn on some pathways and turn off others. They direct cells to grow, shrink, move, stop and die. Drugs that activate or inhibit kinases are an important cancer treatment. They target cell pathways and are more sophisticated than cell-death-promoting chemotherapy.

5. With the advent of cancer genome sequencing, mutations in each gene can be identified. Though unique to every person, cancer pathways will have commonality. Drugs that target these pathways will be the future of cancer treatment.

A whole lot of marvellous things have happened in cancer medicine since 2010 and I am very glad that Mukherjee has updated his book with four new chapters.

The developments that interest me the most are that:

1. The six hallmarks of cancer have three more features added to them. Cancer cells reprogram energy metabolism. They avoid detection by the immune system and thus evade immune destruction. The genetic makeup of cancer cells is unstable and keeps changing.

2. Carcinogens or mutation causing chemicals prime the cell but then an inflammatory event is needed as a catalyst to trigger cancer. Chemicals that cause inflammation are called inflammogens.

3. The standard model of carcinogens might be wrong. It could be that  tumours don't evolve from exposure to a carcinogen. It is possible that the original mutant cells are already within us as “sleeper cells awaiting activation.” When exposed to a carcinogen it is possible that the mutant cells become active and cancer is triggered.

4. T cells are immune cells that attack invaders. They have an off switch that controls their own response to stop them from turning on their own cells. Cancer cells trick T cells into believing that they are harmless. By blocking those signals cancer cells are made visible again. This is the heart of immune therapy.

   
   

5. Where Mukherjee once thought that genomics would be the focus of targeted personalised therapies this focus has shifted to organoids. Scientists are growing cancer cells from patients in the form of three-dimensional cellular structures that replicate living tumours. They are testing drugs to find what works on the organoids before applying them to patients. This might be the future of precision medicine.

What was once a death sentence is now in many cases a curable illness. This book tells of the slow progression to that point, starting in 2500 BC when there was a hieroglyph for cancer but no treatment. It finished in 2025 in an era of knowledge, of progress, of hope. If anyone in your life has cancer, I recommend that you read this book.