Acknowledgements
Development of the new Clinical Practice Guidelines for the Diag-
nosis and Management of Melanoma was undertaken by Cancer
Council Australia and Melanoma Institute Australia, and supported
by the Skin Cancer College Australasia and the Australasian Col-
lege of Dermatologists. The authors thank the staff of the Cancer
Council Australia Clinical Guidelines Network for their invaluable
guidance and support. In particular we thank Tamsin Curtis for
coordinating the melanoma guidelines revision process and Cecilia
Taing for undertaking the systematic literature review that provided
the evidence on which this article was based.
Reference
1. Cancer Council Australia Melanoma Guidelines Working Party. Clinical
Practice Guidelines for the Diagnosis and Management of Melanoma.
[Cited 17 Jul 2019.] Available from URL: https://wiki.cancer.org.au/
australia/Guidelines:Melanoma
Michael A. Henderson,*† MD, FRACS
John Spillane,*† MBBS, FRACS
T. Michael Hughes,‡ MBBS (Hons), FRACS
Andrew J. Spillane,§ MD, FRACS
B. Mark Smithers,k MBBS, FRACS
John F. Thompson,¶ MD, FRACS
*Peter MacCallum Cancer Center, Melbourne, Victoria, Australia,
†Department of Surgery, The University of Melbourne, Melbourne,
Victoria, Australia, ‡Sydney Adventist Hospital, The University of
Sydney, Sydney, New South Wales, Australia, §Melanoma Institute
Australia, Royal North Shore Hospital, The University of Sydney,
Sydney, New South Wales, Australia, ¶Queensland Melanoma
Project, Princess Alexandra Hospital, The University of
Queensland, Brisbane, Queensland, Australia and kMelanoma
Institute Australia, The University of Sydney, Sydney, New South
Wales, Australia
doi: 10.1111/ans.15407
Organoids: the new kid in cancer research
Cancer is a major health burden and is expected to rank as the lead-
ing cause of death in every country in the 21st century.
1
Despite
extensive research and advances in cancer care, there is significant
limitation in translation of bench to bedside treatments, largely due
to the nature of current cancer models used in research.
Current cancer models include cell lines and mouse xenografts
(PDXs). Cancer cell lines are two-dimensional models of cells
grown in vitro. They have variable success in establishment, often
undergo substantial in vitro genetic changes and fail to recapitulate
the heterogeneity of the native tumour. Xenografts on the other
hand retain the biology of the tumour better than cell lines. How-
ever, they are expensive, time and resource intensive, have variable
success in establishment and may develop mouse-specific tumour
changes over time.
2
While both have been immensely useful in
basic science, they have significant limitations in their clinical
applicability. Recently, the development of a more physiological
pre-clinical model that overcomes many of the deficiencies of cell
lines and PDXs has come to the fore. Dubbed by Nature magazine
as ‘the method of the year’, novel cancer models called ‘organoids’
have the potential to revolutionize cancer care.
Organoids are three-dimensional (3D) cultures of cancer cells
grown in the laboratory that recapitulate tumour heterogeneity and
maintain genomic integrity far better than cell lines and animal
models. Tumour-specific stem cells can grow from small pieces of
tumour embedded in a synthetic extracellular matrix in a cell cul-
ture plate with a cocktail of growth factors into self-organizing and
self-sustaining 3D structures called organoids.
3
Organoids represent
the native cancer in their mutations, physiology and their cellular
interactions. These ‘mini tumours’ can be rapidly grown in a matter
of days, with greater success rates than cell lines or mouse models.
4
Organoids have enormous clinical applicability and potentially rep-
resent the next frontier in changing cancer care for patients.
Organoids can be grown with high success rates from simple
needle biopsies. To date, organoids have been successfully devel-
oped from numerous cancers, including colorectal, pancreatic, gas-
tric, oesophageal, liver, lung, glioblastomas and testicular cancers.
5
They can be used to develop a ‘living tumour biobank’ wherein
replenishable organoids can be stored for each cancer.
Organoids can be used to help predict and prognosticate patient
responses to therapy. Early studies with rectal cancer have shown
that organoids can help predict rectal cancer responses to
chemoradiotherapy.
6
This could potentially change how we treat
rectal cancer in the future. They can be used to model and study
various diseases, from genetic disorders like cystic fibrosis
to inflammatory conditions like Clostridium colitis.
7
The ability to
also grow matched ‘normal’ tissue organoids allows one to interro-
gate the genetic alterations that lead to cancer, with gene editing
tools like CRISPR-Cas9 that can be used to switch genes on
and off.
8
Immunotherapy has transformed the treatment landscape of can-
cers such as melanoma and renal cell carcinoma. Currently, there
are no reliable biomarkers to predict responses to immunotherapeu-
tic drugs. Organoids provide a valuable strategy to evaluate the
response to immunotherapy in patients, thereby selecting those
likely to respond to immunotherapy, and avoiding immunotherapy
related complications in non-responders.
9
One of the most promising areas for the utilization of organoids
is in drug development and personalized medicine. Many drugs fail,
or take years to reach the clinic due to regulations regarding evalua-
tion of the drugs toxic profile. With the ability to grow normal
Perspectives 1189
© 2019 Royal Australasian College of Surgeons