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02
Nov
2020

The progression of cancer throughout history


James Watson and Francis Crick with their DNA model. Photo: Science History Institute

Throughout human civilisation, the presence of cancer can be traced back as far as 3,000 BC. Much has been learned about the different types of cancer since then, and we have made great advances in treating those impacted by the disease. 

Cancer is not a modern malady. Fossilised bones and the mummies of Egypt show evidence of tumours, and a written description of cancer has been found in an Egyptian papyrus dating back to 3,000 BC. The ancient surgical manuscripts describe eight cases of breast cancer and the scripts bleakly note, “There is no treatment.”

For most cancers, this is no longer the case. Today in Australia, approximately 70 per cent of people diagnosed will survive beyond five years after diagnosis. Sadly, for brain cancer, five-year survival is languishing at 20 per cent, a figure that has not shifted for more than 30 years. 

 

The overall increases in survival for most cancers can be accredited to the explosion of our understanding of the disease. However, in the immortal words of Sir Isaac Newtown, “If I have seen further it is by standing on the shoulders of giants”. Researchers of today also owe much to the scientists and doctors of the Renaissance and 18th and 19th centuries, who laid the foundations of modern-day epidemiology and cancer treatment.

The presence of cancer can be traced back as far as 3,000 BC, a similar time to the completion of the Great Pyramids.

Advances in understanding the causes of cancer

Hippocrates (460–370 BC) is credited with coining the term carcinoma, and for hypothesising that cancer was caused by “an imbalance of the four humors”. 

Countless theories of what causes cancer have been proposed, including:

  • Angering of the Gods
  • Fermenting or acidic lymph
  • Chronic irritation, trauma, and infection 

These theories stood unchallenged until the Renaissance, when Galileo and Newton began to use the scientific method, which laid the foundations for the modern study of disease.  

The 18th century saw the birth of cancer epidemiology when three insightful observations were made. Firstly, the high incidence of breast cancer in nuns compared to non-celibate women gave the first hint that hormones may play a role in cancer. Soon after, descriptions of cancer commonly in the scrotum of London’s chimney sweepers led to public health measures to reduce a person’s cancer risk at work. Finally, a book was published linking tobacco use with cancer, which laid the foundations for the US Surgeon General’s 1964 warning that smoking caused lung cancer.

Fast forward nearly 200 years to 2012, and the World Health Organization’s International Agency for Research on Cancer (IARC) identified more than 100 chemical, physical, and biological carcinogens (the agents that cause cancer by damaging DNA or disrupting cell metabolism).

The genetics of cancer

We now know that cancer is a disease caused by damaged DNA. In the 67 years since James Watson and Francis Crick solved the structure of DNA, giving the world the iconic double helix, the pace of change in the field of cancer genetics has been dizzying. Much of Watson and Crick’s success can be attributed to Rosalind Franklin’s ground-breaking imagery of DNA, enabling Watson and Crick to create their famous two-strand DNA model. 

During the 1970s, scientists discovered oncogenes (genes that cause cells to grow out of control and become cancer cells), and tumour suppressor genes (normal genes that, when damaged, cause cells to grow out of control, potentially leading to cancer). 

DNA sequencing technology became so sophisticated and efficient that by the early 1990s, the human genome project (a project devoted to decoding the entire genome) was proposed. Decoding that first genome involved thousands of DNA sequencing machines, cost several billion dollars, and took almost 15 years to complete.

By comparison, modern DNA sequencing technologies are fully automated and can generate 200‐300 billion bases of DNA sequence per run. This is equivalent to the genomes of 30 people in just a few days with costs in the mere hundreds of dollars. Personalised medicine (sequencing a patient’s genome and tailoring a treatment program based on their genetic profile) shows inordinate promise for cancer patients.

Today, research into the genetics of cancer is at the forefront of research in various facets of the disease, including brain cancer. In fact, Cure Brain Cancer Foundation currently supports an Australian-based clinical trial called BIOMEDE that aims to uncover these gene changes. The tiral is investigating cancer genetics to develop personalised treatments for children impacted by high-risk brain cancer. Such cancer types include diffuse intrinsic pontine glioma (DIPG), the deadliest form of brain cancer in children.

In March last year a study conducted by researchers at the German Cancer Research Center identified key genetic changes that result in the development and evolution of glioblastoma, the most common and aggressive form of brain cancer.

A brief history of cancer treatment

Surgery

Humans have always performed surgery on one another. The Roman physicians knew that cancer could be treated with surgery, and remarked, “After excision, even when a scar has formed, none the less, the disease has returned”. But it was not until the discovery of anaesthesia and aseptic techniques that surgery became anything but a terrifying last resort for the cancer patient.

The first radical mastectomy to treat breast cancer was performed in 1880, but more conservative methods of cancer resection were not developed until the 1970s when the total mastectomy and later lumpectomy were shown to be just as effective for treating early breast cancer. The trend for removing less healthy tissue extended to treating bone and soft tissue cancers of the limbs without the need for amputation, and rectal cancer without the need for colostomy.

The late 20th century saw the development of lymph node biopsies, and fibre optic technology and advances in imaging have reduced the need for exploratory surgery, allowing for precise tumour localisation, biopsy and removal, and reducing the risk of postoperative side effects.   

Radiation Therapy

Proton Beam Therapy in action. Image: Tomi Australia

The 1901 Nobel Prize in physics was awarded to Wilhelm Conrad Roentgen for his discovery of what he called the “X-ray”, with “X” being the algebraic symbol for an unknown quantity. The turn of the 20th century also saw Marie and Pierre Curie’s discovery of radium and polonium, and their coining of the word ‘radioactivity’.  Remarkably, within a couple of years, two Russian skin cancer patients were successfully treated with radiation therapy. Radiation therapy remains a mainstay of modern cancer treatment.

Driven by computer and imaging technology, we’ve seen a game changing shift towards more precise, targeted radiation therapy during the past couple of decades. The development of intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT) means radiation beams can be matched to the shape of the tumour and delivered from several directions reducing side effects. For some cancers this provides cure rates equivalent to surgery.

The modern-day advance in proton beam therapy now offers new hope to those impacted by brain cancer. This form of treatment delivers a precise amount of radiation directly to tumours, minimising the risks and side effects associated with traditional radiotherapy. By the end of 2020, it's estimated more than 200,00 patients will have been treated with proton therapy for various types of cancer. 

Australia’s first proton therapy unit is currently being built in Adelaide. Once built, it will be the most advanced proton therapy centre in the Southern Hemisphere. The Australian Bragg Centre for Proton Therapy and Research is to be housed within the new SAHMRI 2 building in Adelaide’s centre. This 14-story building will also be home to research laboratories and biomedical companies.

The Australian Bragg Centre aims to provide proton therapy for 800 patients per year. They hope to be open and treating the first patients by 2022. 

Chemotherapy


Modern day chemotherapy treatment. 

The chemotherapy era began during World War II when it was discovered that soldiers exposed to nitrogen mustard (a compound of mustard gas) died because their bone marrow was destroyed. Subsequent research found it killed rapidly dividing cells (such as cancer cells) by destroying their DNA. Interfering with cell division by damaging DNA causes cells to commit suicide (apoptosis), which remains the underlying principle of chemotherapy.

Despite advances in chemotherapy during the 1950s and '60s, surgery and radiotherapy continued to dominate oncology until it became clear that cure rates plateaued at about 33 per cent. The realisation that chemotherapy could be used in conjunction with surgery and radiation was pivotal in improving patient survival.

Chemotherapy is now tailored to a cancer’s molecular profile, stage, response to previous treatments, and often to the patient’s specific genetic profile. Dozens of combinations of drugs are proven to improve patient survival.  

Immunotherapy

In the 1850s, physicians noticed that tumours would occasionally shrink if they became infected. This led to the idea that the patient’s immune system could be harnessed to fight cancer cells. Progress in immunotherapy was slow until Cambridge scientists first synthesised antibodies in the 1970s. Antibody synthesis, together with expanding knowledge of the immune system, eventually led to the development of modern immunotherapy protocols for cancer. 

Immunotherapy has been identified as a new potential treatment option for brain cancer, which has barely seen an improvement in survival for more than 30 years. Backed by a $200k co-investment from Cure Brain Cancer Foundation and Love for Lachie, the NICHE-HGG  trial will give Australian children with high-grade glioma (HGG) - one of the deadliest forms of brain cancer - access to a promising new immunotherapy treatment.

Modern day survival rates

 

Until the last few decades, cancer was a death sentence. During the 1970s, only about one in two people diagnosed with cancer survived beyond five years. Today, highly tailored, effective treatments target the genetics of each cancer, and each patient. For many cancers survival rates top 90 per cent.

However, the outlook remains bleak for rarer cancers and brain cancer survival rates have barely changed in the last 30 years. Glioblastoma, which is the most common and aggressive form of brain cancer, has a five-year survival rate of just 4.6 per cent.

It is our hope that brain cancer may be eminently survivable in the not too distant future. Donations have enabled Cure Brain Cancer Foundation to invest more than $22 million into world-class research since 2013, including $8 million for projects to help kids with brain cancer. We've backed 53 game-changing research projects, supported Australia’s best scientists and clinicians, and taken brain cancer from a forgotten disease to a national health priority. Our pioneering research strategy means that we can support the world’s most promising brain cancer projects, right here in Australia. 

If research funds are secured, we can expect brain cancer treatments to accelerate with a rate of change like what we have already witnessed. History teaches us that the future holds great promise. 

References 

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