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Page 78 Shek et al. Cancer Drug Resist 2019;2:69-81 I http://dx.doi.org/10.20517/cdr.2018.20

nonsynonymous somatic mutations (n ≥ 302) resulted in improved efficacy of pembrolizumab treatment,
as indicated by a more durable clinical benefit, higher objective response rate (ORS) and PFS (P = 0.02). It
was demonstrated that an increase in the number of somatic mutations increased the production of T cell-
reactive neoantigens. Because these tumour neoantigens are recognized as foreign, they stimulate a stronger
[79]
T-cell immune response, particularly in combination with anti-PD-1 mAb treatment .

CONCLUSION
In summary, the influence of genetic background on cancer treatment is not limited to chemotherapies.
mAb efficacy and metabolism can be significantly impacted by host genetics, whether it be non-synonymous
mutations altering protein structure and function or promoter mutations affecting gene regulation. Host
polymorphisms can also affect mAb target binding, thus significantly affecting treatment efficacy. Key
mutations within critical signalling pathways can affect overall and progression free survival, as well
as treatment response and treatment-related toxicity. Pharmacogenetics is an essential tool to recognise
the association between such germline or somatic mutations and efficacy or toxicity of mAbs in cancer
treatment. It provides the potential to personalize cancer therapy with mAbs and other chemotherapies
with respect to drug choice, drug combination, and dosing. A better understanding of pharmacogenetics
in cancer treatment will undoubtedly benefit existing treatment protocols by implementing new genetic
screening methods such as NGS into clinical practice prior to treatment initiation. Such screening will allow
physicians to predict drug pharmacokinetics and pharmacodynamics, as well as choose the most appropriate
mAb treatment for individualised cancer management.

DECLARATIONS
Authors’ contributions
All authors made substantial contributions to conception and design of the study and performed data
analysis and interpretation.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

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

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

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