TY - JOUR
T1 - The double-edged sword of cancer mutations
T2 - Exploiting neoepitopes for the fight against cancer
AU - Alvarado-Cruz, Isabel
AU - Meas, Rithy
AU - Paluri, Sesha Lakshmi Arathi
AU - Carufe, Kelly Estelle Wheeler
AU - Khan, Mohammed
AU - Sweasy, Joann Balazs
N1 - Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.
PY - 2020
Y1 - 2020
N2 - Defects in DNA repair have been linked to the accumulation of somatic mutations in tumours. These mutations can promote oncogenesis; however, recent developments have indicated that they may also lead to a targeted immune response against the tumour. This response is initiated by the development of new antigenic epitopes (neoepitopes) arising from mutations in protein-coding genes that are processed and then presented on the surface of tumour cells. These neoepitopes are unique to the tumour, thus enabling lymphocytes to launch an immune response against the cancer cells. Immunotherapies, such as checkpoint inhibitors (CPIs) and tumour-derived vaccines, have been shown to enhance the immunogenic response to cancers and have led to complete remission in some cancer patients.There are tumours that are not responsive to immunotherapy or conventional tumour therapeutics; therefore, there is a push for new treatments to combat these unresponsive cancers. Recently, combinatorial treatments have been developed to further utilise the immune system in the fight against cancer. These treatments have the potential to exploit the defects in DNA repair by inducing more DNA damage and mutations.This can potentially lead to the expression of high levels of neoepitopes on the surface of tumour cells that will stimulate an immunological response. Overall, exploiting DNA repair defects in tumours may provide an edge in this long fight against cancer.
AB - Defects in DNA repair have been linked to the accumulation of somatic mutations in tumours. These mutations can promote oncogenesis; however, recent developments have indicated that they may also lead to a targeted immune response against the tumour. This response is initiated by the development of new antigenic epitopes (neoepitopes) arising from mutations in protein-coding genes that are processed and then presented on the surface of tumour cells. These neoepitopes are unique to the tumour, thus enabling lymphocytes to launch an immune response against the cancer cells. Immunotherapies, such as checkpoint inhibitors (CPIs) and tumour-derived vaccines, have been shown to enhance the immunogenic response to cancers and have led to complete remission in some cancer patients.There are tumours that are not responsive to immunotherapy or conventional tumour therapeutics; therefore, there is a push for new treatments to combat these unresponsive cancers. Recently, combinatorial treatments have been developed to further utilise the immune system in the fight against cancer. These treatments have the potential to exploit the defects in DNA repair by inducing more DNA damage and mutations.This can potentially lead to the expression of high levels of neoepitopes on the surface of tumour cells that will stimulate an immunological response. Overall, exploiting DNA repair defects in tumours may provide an edge in this long fight against cancer.
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U2 - 10.1093/MUTAGE/GEZ049
DO - 10.1093/MUTAGE/GEZ049
M3 - Review article
C2 - 31880305
AN - SCOPUS:85079344344
SN - 0267-8357
VL - 35
SP - 69
EP - 77
JO - Mutagenesis
JF - Mutagenesis
IS - 1
ER -