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Table 2. Summary of SNPs’ influence on cancer treatment with mAbs
SNP Gene Examined drugs Type of cancer Consequences
rs699947 (AA) VEGF Bevacizumab (in Metastatic EGFR-2 negative Higher treatment response and OS
combination with breast cancer
paclitaxel)
rs833061 (TT) VEGF Bevacizumab (in Metastatic colorectal cancer Reduced PFS
combination with folinic
acid, fluorouracil and
irinotecan)
rs121913529 KRAS Bevacizumab Metastatic colorectal cancer Reduced PFS and OS
(KRAS G12A/V)
rs113488022 BRAF Cetuximab, Panitumumab Colorectal cancer Early lymph node metastasis, lower
(BRAFV600E) response
rs4143815 (CC) PD-L1 Nivolumab Non-small cell lung cancer Higher PFS
rs4553808 (G) CTLA-4 Ipilimumab Metastatic melanoma Higher response, associated with
rs11571317 (T) grade 3-4 immune-related adverse
rs231775 (A) events
rs2282055 (GG) PD-L1 Nivolumab Non-small cell lung cancer Higher median of PFS
rs396991 (G) FcgR3A Trastuzumab HER-2 positive breast cancer Higher response rate
Cetuximab Colorectal cancer, Increase response rate and PFS
Rituximab B-cell lymphoma
rs733618 (G) CTLA-4 Ipilimumab, Tremelimumab Metastatic melanoma Higher response rate
rs4553808 (G) CTLA-4 Ipilimumab Metastatic melanoma Higher risk of endocrine immune-
related adverse events
rs733618 (G) CTLA-4 Ipilimumab Metastatic melanoma Higher long-term survival at 3-4
rs3087243 (G) years, comparing to heterozygous
rs17849079 (T) PIK3CA Cetuximab, Panitumumab Metastatic colorectal cancer Poor objective response rate, lower
rs7640662 (C) OS and PFS
SNPs: single nucleotide polymorphisms; PFS: progression-free survival; OS: overall survival

rs5742909 (-319C>T, promoter), rs11571316 (-1577G/A), rs11571317 (-658C>T, 5’UTR) and rs3087243
(CT60G>A, 3’UTR) in 14 patients with metastatic melanoma treated with ipilimumab or tremelimumab.
[74]
It was detected that 83% (5/6) of responders possessed the rs733618 G genetic variant of CTLA-4 gene .
It was also reported, that all responders had diplotype GG - AA (-1577G/CT60G and -1577A/CT60A). In
addition, the rs3087243 heterozygous of CTLA-4 gene was correlated with better 5-year survival, compared
to patients with homozygous genotype (P < 0.001). In this study, all other CTLA-4 SNPs were not statistically
correlated with response to the treatment or OS . In a more recent study by Queirolo et al. , patients with
[75]
[74]
stage IV melanoma, treated by ipilimumab, possessing rs11571316 (-1577G/A) and rs3087243 (CT60G>A)
homozygous genotypes had better long-term survival at 3 and 4 years, compared to heterozygous (G/
A) genotypes. Because patients with the homozygous GG genotype possess reduced CTLA-4 mRNA and
[76]
protein expression, it was suggested that the efficacy of ipilimumab was increased in these individuals . In
[77]
addition, a 2018 study by Queirolo et al. , found that the rs4553808 (-1661G/G) was higher among patients
with endocrine immune-related adverse events (irAEs) but not cutaneous or gastrointestinal adverse events.

The future of monoclonal antibody therapies: personalised care?
Current data suggests that mAbs are effective and specific anticancer drugs, however their efficacy and
toxicity have demonstrated significant variability due to genotypic differences relating to mAb recognition,
metabolism and cancer signalling. Consequently, next-generation sequencing (NGS) technologies, and
particularly whole-genome sequencing (WGS) and whole-exome sequencing (WES) will prove to be
invaluable as mAbs become more widely used. While WGS sequences the genome in its entirety (> 95%),
WES sequences only transcribed regions, and is therefore significantly faster and cheaper. Nonetheless, WGS
captures significantly more information, as it can identify significant mutations that are not transcribed such
as promoter regions. As the cost of NGS decreases, usage will increase, thus allowing the identification of the
full range of somatic mutations present in cancerous and non-cancerous tissue, and allowing physicians to
decide on the best therapeutic options .
[78]
A prime example of NGS research into mAb therapies was performed by Rizvi et al. , who performed
[79]
WES on non-small cell lung cancers treated with pembrolizumab. Paradoxically, a higher number of