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independent roles in determining APN levels [219] . This is important to consider as a therapeutic agent may
have greatly differing effects across individuals. Secondly, the pleomorphic nature of APNs isoforms mean it
will be hard to replicate each isoforms action. One option would be to use recombinant APN, however this
has been difficult to produce and would be expensive over the long term. The solution has been to attempt
to increase endogenous APN, but we must consider whether it may be beneficial to selectively increase one
isoform. Thirdly, the dosage APN used can affect the inflammatory response in a varied manner. In creating
a novel agent, the dose regime must be carefully designed to ensure the desired response is seen.

CONCLUSION
Obesity related-cancers are now a recognised phenomenon. APN is the key adipokine produced by the fat cells
and its role in cancer pathogenesis and disease prognosis is now slowly revealed. Hypoadiponectinaemia is often
found to be associated with cancers and also affects their prognosis. Therefore, various efforts have been made
to harness its therapeutic effects. It can be applied either therapeutically or prophylactically to treat various
cancers. For example, identification of ADIPOQ, AdipoR1 and AdipoR2 SNPs that may confer altered risks of
cancer development may enable early screening and APN level augmentation via therapeutic interventions.

Overall this field holds a huge promise, however many challenges will need to be addressed prior to its routine
use. Cellular and molecular function of APN in cancer either its pathogenesis phase or advanced forms of
cancer will need to be fully researched. APN may have different effect on various stages of cancers either
directly or indirectly via immune system. The role of each isoform in distinct tissues and under specific
conditions needs be clarified. More importantly, the molecular conditions under which APN acts as cancer
suppressing or promoting and anti-inflammatory or pro-inflammatory still needs to be fully evaluated. The
exact roles of APN interacting which receptors (some identified but some remained to be defined) and their
downstream pathways in different cancer have largely remained elusive. Exploring an effective APN-based
therapeutic and when to applied this therapeutic may be the crucial step. Understanding the complexity of
APN on anti-tumour response may need to be considered when using it as a therapeutic agent.

DECLARATIONS
Acknowledgments
Due to the space restrictions, the authors were able to cite only a fraction of the relevant literature. We
apologize to any colleagues whose contribution might not be appropriately acknowledged in this review.

Authors’ contributions
Wrote and prepared most of the manuscript: Monks M
Contributed toward the revision of manuscript: Irakleidis F
Provided guidance and mentorship to all authors in writing and revising the manuscript: Tan PH

Availability of data and materials
Not applicable.

Financial support and sponsorship
Tan PH is funded by Royal Free NHS Foundation Trust as a full-time Consultant Oncoplastic Breast
Surgeon.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.