Newsletter March
2024: A Review of 2023
1.
Cancer deaths continued to decline, but
it is way too soon to be complacent
Cancer trends in the US are published annually by the American
Association of Cancer Research. The latest update was published in January
2024.[i]
Once again they showed a decline in the US death rate, continuing a trend since
1991, that has now reached a total of over 4 million fewer deaths since 1991.
This downward trend is primarily driven by reductions in smoking, earlier
detection for some cancers, and improved treatment options.
But it is too soon to be complacent. The statistics showed an increase in
incidence rate. Especially alarming is
the continuing increase in cancer diagnoses in adults under 50 years old.
This is most notable in colon cancer[ii],
but extends to some other cancers as well.
And talking about not being complacent, there is also the latest global projection
from the World Health Organisation.[iii]
Cancer cases around the world are expected to surge 77% by 2050. This is
based on an analysis of 185 countries, which cites a growing, aging population as
well as factors including tobacco, alcohol, obesity, and pollution.
2.
Standout areas in 2023
There were two main standout areas in 2023; an explosion in the new class
of drugs called antibody drug conjugates, and the migration of Immunotherapy to
earlier stage disease.
2.1.
Antibody Drug Conjugates (ADC’s) – a new
treatment modality and an explosion of new drugs
ADCs add a new option for cancer treatments,
indeed a new class of cancer drugs.
·
Usually, chemotherapy is delivered as a systemic
drug, a drug which circulates throughout the body and attacks all fast-dividing
cells. This covers cancer cells, but also attacks other fast-growing cells like
hair, gut lining, immune cells etc. So, chemo is somewhat inefficient and has lots
of side-effects.
·
An ADC, on the other hand, is a manufactured assembly,
tailor-made to deliver the chemo only to a target uniquely expressed on the
cancer cells; essentially a guided missile
o
It requires a target (any target) which is
uniquely expressed on the cancer cells
o
An antibody is then identified to specifically track
and engage the target (an intelligent missile head)
o
This antibody is linked (a linker) to a dose of
chemo (the payload).
o
The linker is designed to release its payload only
when the antibody is engaged.
This means it is no longer necessary to
find the genes driving the cancer. Instead, one can use nearly any protein on a
cancer’s surface—so long as it isn’t commonly expressed on normal cells—to
deliver chemotherapy through this highly potent antibody-drug conjugate. This means
the drug is more efficient and there are less side effects.
As of mid-2023 around 10 ADC’s had been
approved for various cancers, and currently more than 100 ADC candidates are in
different stages of development and clinical testing.[iv]
2.2.
Immunotherapy to earlier stage disease
This was covered in Blog 5 in May
last year under the heading “IO to reduce the risk of recurrence in
earlier-stage cancers”.
It is becoming increasingly clear
that IO for earlier stage disease should be administered up-front, prior to
surgery (this is called neoadjuvant treatment); the advantages of this are:
i.
It maximises the opportunity for the effective
priming of the immune system to be able to see and attack any cancer cells
which may remain after surgery.
ii.
It can improve surgical outcomes by shrinking
the size of the tumour before surgery, and
iii.
It can potentially make surgery unnecessary in
some cases by completely eliminating the tumour through IO.[v]
Currently, neoadjuvant
immunotherapy has only two approved indications: triple-negative breast
cancer and resectable non-small cell lung cancer, although numerous trials
are in progress, including for Melanoma and Colon cancer.
2.3.
Some other areas to watch:
i.
Cancer Vaccines: There is a continuing focus
on developing cancer vaccines to help the immune system see cancer cells. For
example, a phase 3 trial has recently been launched to assess a personalised
mRNA cancer vaccine (based on the technology used for the COVID vaccine) in
combination with an immune checkpoint drug for high-risk melanoma aiming for
availability in 2025[vi].
And 2024 is seen as a potential breakthrough year for cancer vaccines, looking
for ways to turn cold tumours hot.[vii]
ii.
Liquid biopsy is fast moving into routine
practice, a significant opportunity not only in early treatment
planning, but more so in testing for minimum
residual disease after surgical removal of localised disease.[viii]
If residual disease is found by liquid biopsy after surgery, then further
treatment is required.
[ii] Colorectal Cancer Risk Increasing Across Successive
Birth Cohorts - Medscape - January 30, 2024.
[iii] Global cancer burden
growing, amidst mounting need for services - WHO News Release, February 2024
[iv] ADCs Make Their Mark
- Cancer Today, June 2023
[v] Immunotherapy and… Nothing Else? Studies Test Potential
Paradigm Shift in Cancer Treatment - National Cancer Institute, Feb 2023
[vi] Coming Soon: The First mRNA Vaccine for Melanoma? -
Medscape - January 17, 2024.
[vii] Experts Forecast 2024, Part 1: Advances in Cancer Vaccines -
AACR, Jan 2024
[viii]
The
Promise of Liquid Biopsies - Cancer Today, AACR, Sept 2023