TY - JOUR
T1 - Exposing Hidden Targets
T2 - Combining epigenetic and immunotherapy to overcome cancer resistance
AU - Olino, Kelly
AU - Park, Tristen
AU - Ahuja, Nita
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/10
Y1 - 2020/10
N2 - Advances in immunotherapy, most notably antibodies targeting the inhibitory immune receptors cytotoxic T-lymphocyte associated protein 4 (CTLA-4/CD152), programmed death protein 1 (PD-1/CD279) and programmed death-ligand 1 (PD-L1/B7H1/CD274) have become effective standard therapies in advanced malignancies including melanoma,1–4 merkel cell carcinoma5, urological cancers6–8, non-small cell lung cancer9–11, mis-match repair (MMR) deficient tumors12, and Hodgkin lymphoma with response rates ranging from 25 to 60% in the first and second line settings13,14. FDA approval has also been given for treatment for hepatocellular carcinoma, gastric cancer, triple negative breast cancer, cervical and head and neck cancers with response rates closer to 15 %15. Additionally, some clinical efficacy has been observed in ovarian cancer, mesothelioma, prostate cancer, diffuse large B cell lymphoma, follicular lymphoma, and both cutaneous and peripheral T-cell lymphoma. However, despite these successes, most patients will initially fail to respond to treatment and almost half of initial responders will develop secondary resistance to immunotherapy and progress. Moreover, many prevalent solid organ tumors remain resistant to immunotherapy including colorectal, pancreatic and hepatobiliary cancers. Therefore, new therapies are needed to increase both initial and durable response rates and to develop new mechanistic insights into pathways of immune resistance so that immunotherapy may become more widely available as a therapeutic option in common malignancies.
AB - Advances in immunotherapy, most notably antibodies targeting the inhibitory immune receptors cytotoxic T-lymphocyte associated protein 4 (CTLA-4/CD152), programmed death protein 1 (PD-1/CD279) and programmed death-ligand 1 (PD-L1/B7H1/CD274) have become effective standard therapies in advanced malignancies including melanoma,1–4 merkel cell carcinoma5, urological cancers6–8, non-small cell lung cancer9–11, mis-match repair (MMR) deficient tumors12, and Hodgkin lymphoma with response rates ranging from 25 to 60% in the first and second line settings13,14. FDA approval has also been given for treatment for hepatocellular carcinoma, gastric cancer, triple negative breast cancer, cervical and head and neck cancers with response rates closer to 15 %15. Additionally, some clinical efficacy has been observed in ovarian cancer, mesothelioma, prostate cancer, diffuse large B cell lymphoma, follicular lymphoma, and both cutaneous and peripheral T-cell lymphoma. However, despite these successes, most patients will initially fail to respond to treatment and almost half of initial responders will develop secondary resistance to immunotherapy and progress. Moreover, many prevalent solid organ tumors remain resistant to immunotherapy including colorectal, pancreatic and hepatobiliary cancers. Therefore, new therapies are needed to increase both initial and durable response rates and to develop new mechanistic insights into pathways of immune resistance so that immunotherapy may become more widely available as a therapeutic option in common malignancies.
KW - Cancer
KW - Epigenetics
KW - Immune resistance
KW - Immunotherapy
KW - Precision medicine
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U2 - 10.1016/j.semcancer.2020.01.001
DO - 10.1016/j.semcancer.2020.01.001
M3 - Review article
C2 - 31911188
AN - SCOPUS:85077658440
SN - 1044-579X
VL - 65
SP - 114
EP - 122
JO - Seminars in Cancer Biology
JF - Seminars in Cancer Biology
ER -