Drugs for Cancer Flashcards
This lecture
The broad epidemiology of cancer
Why it’s hard to find evidence of cancer in the pre-science world
Ideas about cancer origins and treatment before scientific
medicine
How early scientific medicine grappled with cancer and its
transmission
How chemotherapy was developed
The pros and cons of chemotherapy in cancer treatment
The cultural impact of cancer and its treatment
Future directions
Learning Outcomes
To describe the broad global epidemiology of cancer.
To describe pre-science beliefs about cancer and its origins, spread, and
treatments.
To describe how the first chemotherapy treatment was developed.
To describe the social, cultural, and medical impacts of the discovery of
chemotherapy
What is
cancer?
The abnormal growth of cells within the body to the point
where they become malignant and invasive
Ranks among the most feared human diseases. Usually originates inside the human body where it is unseen. Is often only detected after it is too late for successful treatment. Cancer is a leading cause of death in developed countries: An ‘old person’s’ disease? You have to survive long enough to
develop some cancers.
In Western history, and in developing countries today, other diseases
will usually end a person’s life earlier, eg. infectious diseases, infant
mortality, death in childbirth
Humerus –
possibly female,
Central
America,
1300CE?
Possible
sarcoma
Cancer the Crab
In traditional astrology, Cancer was a star sign
indicated by a giant crab.
The Babylonians thought it was a turtle, and the
Egyptians thought it was a scarab beetle.
The constellation Cancer is one of the faintest in
the sky.
Cancer’s alleged astrological characteristics are
darkness, sinister behaviour, sideways creeping,
gnawing, and secrets.
Archaeology
and prehistory
It’s hard to find signs of cancer in ancient human remains.
This is also why some academics argue that cancer was rarer in the
past than it is today.
Some possible signs of cancer have been found in ancient
Egyptian mummies and in fossilised human bones.
But we can’t always tell whether these are truly cancerous
(i.e malignant), or benign tumours.
They could even simply represent skeletal erosion from the
elements.
Cancer can also affect muscles and organs, and these are generally
not preserved for archaeologists to discover.
No bog bodies or ice-men yet!
Why ‘cancer’?
Original Greek word καρκινος
(karkinos), used in the Hippocratic
Corpus, which originally meant
‘crayfish’ or ‘crab’.
Tumors can make a round shape
under the skin and stretch the veins
- like a crab with its legs radiating
outwards from its body.
The condition also caused gnawing
pain like a crab.
Hippocratic text The Aphorisms:
‘Itis better not to apply any
treatment in cases
of occult [hidden] cancer; for, if
treated, the patients die quickly;
but if not treated, they hold out for
a long time’ (Section IV, no 38)
Celsus and cancer
The Roman physician Celsus
translated καρκινος as carcinos
We use this word today: a carcinogen is a
chemical with proven cancer-causing potential.
Celsus identified a range of different cancers in
the body and also their symptomatology.
Recommended aggressive cutting, but only in
the early stage.
Recommended topical treatment for small
superficial cancers: cabbage, a salted mixture of
honey and egg white, or ripe figs.
Both Hippocratic and Roman medicine believed
that cancer was caused by excess of black bile –
purgatives were the best preventive medicine.
Ancient Egypt
The Edwin Smith Papyrus (c1500BCE, and one of the
most famous ancient Egyptian medical codices along with
the Ebers Papyrus) contains a description of what may be
thoracic cancer.
Case 45 describes ‘ball-like tumours’ on a man’s chest
which have spread, feel cold to the touch, and are solid
under the skin.
‘There is no treatment’: the Egyptians knew that cancer
which had spread this far was untreatable.
Cancer in the
classical world
Galen: oncos from theGreek όγκος
which means ‘swelling’ or ‘tumour’
Used today in words like oncology -
the medical specialisation dealing
with cancer
Ibn Sina (Avicenna), Canon of
Medicine : a growth which
‘progressively increases in size, is
destructive, and spreads roots
which insinuate themselves
amongst the tissue-elements.
It does not necessarily destroy
sensation unless it has existed for a
long time, and then it kills the
tissues and destroys the sensation
in the part.’ (Canon of Medicine,
s.213)
Trouble with
the written
records!
Because cancer was mysterious and
elusive, there was no one standard
name for the wide variety of tumours
and growths that can be cancerous.
The English language
took carcinos and turned it into canker,
which meant any type of swollen or
ulcerated sore.
Mouth ulcers are still sometimes
called cankers.
The French word chancre has now
come to mean genital ulcers
associated with syphilis - but it used to
mean any form of spreading ulcer.
What caused cancer?
Many different cultures had their own traditional ideas of what caused cancer.
Humoral theory – black bile.
Islamic cultures emphasised the role of proper diet in preventing cancers.
Medieval European societies believed it could also be contagious and could
spread through the air, or through contact.
This idea persisted well into the early twentieth century in the West.
1926 Nobel Prize
goes wrong!
Danish oncologist Johannes Fibiger (1867-1928)
was awarded the 1926 Nobel Prize for ‘discovering’
that stomach cancer was caused by roundworms.
Gongylonema neoplasticum – but Fibiger named
them Spiroptera carcinoma.
After his death in 1928, other researchers proved
that Fibiger had arrived at the wrong conclusions
about his experiments – roundworms were not
responsible, and the tumours were not cancerous.
Other forms of cancer treatment
Small benign tumours and other neoplasms (new and abnormal
tissue growths) could be removed even with very primitive surgery.
This included full amputation of limbs.
Ancient writers knew it was almost impossible to treat cancer once
it was well-established in the organs.
This included breast cancer.
Medieval physician Jean de Tournemire (1329-1396) said that ‘he had
practiced for forty years and had not seen any woman suffering
this kind of disease being cured
The nineteenth century
Improvements in microscopic technology and antiseptic
surgery improved knowledge of the body’s cells.
However, only slow progress occurred in the understanding
and treatment of cancer.
In 1829, French gynaecologist Joseph Recamier (1774-1852)
described how cancer could spread through the body via the
bloodstream.
He coined the word metastasis (from the Greek term
meaning ‘removal from one place to another’) to describe
this process.
Mustard gas
1914-1918 war: Imperial German Army developed sulphur
mustard, or mustard gas.
Actually a fine droplet mixture that was sprayed into the air –
not strictly a gas.
Had a distinctive peppery odour that evoked comparisons to
garlic, mustard or horseradish.
Mustard gas caused blisters to form on the skin and in the
lungs.
This caused terrible injuries, disability and death to both
humans and animals following battlefield exposure.
Gas masks were issued to soldiers but were not always effective
at saving lives or preventing injury
Lymph? Juice?Cells?
By the mid 19th century, most European researchers believed
that cancer was caused by deteriorating lymph from the lymph
glands.
German scientist and pathologist Rudolf Virchow (1821-
1902) believed that cancer spread via a ‘juice’ released by
primary tumours that somehow converted normal cells at other
sites into tumours.
1840:German surgeon Karl Thiersch (pictured) showed that it
was malignant cells moving throughout the body that caused
metastasis.
This growing knowledge also helped surgeons to be more
efficient in removing all of a cancerous growth from the body
when they operated.
X-rays and cancer
1895: physicist William Roentgen (1845-1923) produced a nowfamous image of his wife Anna Bertha’s hand using a strange new
type of electromagnetic energy which he called theX-ray.
This won him the 1901 Nobel Prize - the first ever awarded for
physics.
X-rays allowed researchers to see inside the human body for the
first time without cutting it open.
They also cured some types of skin cancers and conditions,
including lupus.
However, X-rays also caused cancer in many early experimenters
and their patients.
Ban on gas
warfare – but
was it?
Geneva Gas Protocol 1925 – signed by most
countries, banning the use of chemical and biological
weapons in warfare.
At the time of its signing, several major powers
(including the United Kingdom, France, and
the Soviet Union) explicitly reserved the right to use
the forbidden weapons for retaliatory purposes.
In other words, if a state decide to use chemical or
bacteriological weapons against another
country, the country under attack would legally be
allowed to respond in kind.
So mustard gas was ‘banned but not banned’ …
Mustard gas disaster at
Bari, Italy, 1943
Bari was a British-occupied port in Italy in WWII.
One of 29 US ships waiting to unload their cargo at
Bari carried a secret cargo of mustard gas.
German air attack September 2, 1943.
The merchant vessel John Harvey caught fire - killed
over 1,000 people and exposed many to mustard
gas.
Officially, some 617 mustard gas-related
casualties were recorded at Bari, with at least 84
deaths attributed to the toxic exposures.
The link is made
Lt Col Stewart Alexander, US military doctor, went to Bari
and correctly identified the cause of injuries as mustard gas.
Meticulously studied the survivors and conducted detailed
autopsies on deceased victims.
Observed that mustard gas was toxic towards bone
marrow and destroyed its victim’s white blood cells.
Floated the idea that mustard gas might slow the growth of
tumour cells, especially cancers such as leukaemia that
involve uncontrolled production of abnormal white blood
cells.
JD – the first human trial, Yale
University, 1943
Yale University – Drs Louis Goodman and Alfred Gilman (pictured)
carried out successful animal trials with nitrogen mustard.
JD – anonymous patient with advanced lymphoma - tumours in his jaw,
armpits and chest (considered terminal).
27 August 1942, JD was given ‘synthetic lymphocidal chemical’ or
‘substance X’.
This was nitrogen mustard.
Within a month his cancer was gone – he could sleep, eat, and was in
less pain.
However, his white blood cells had been decimated.
By December 1942, JD was dead.
Early forms of chemotherapy
Early examples included:
antifolates which could induce remission in some types of
lymphoma (cancer of the lymphatic system, part of the body’s
defence mechanism);
alkaloid drugs (including medicines extracted from the vinca
plant);
corticosteroids which were also effective against other forms of
cancer.
In 1965, the first forms of combination chemotherapy were developed which
involved giving two or more anticancer drugs to a patient.
Multidrug combination strategies were soon used widely
The downside of chemotherapy
No one treatment can work for all forms of cancer.
Traditional chemotherapy is fundamentally harmful to patients.
Designed to cause nonspecific DNA damage or inhibit normal cell
processes like cell division and growth.
Chemotherapy has many different side effects such as weight
gain, hair loss, nausea, aches and pains, and feeling unwell.
Some people choose to forgo it and use simply radiation and/or
surgery for a higher quality of life during the last stages of their
illness.
