Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single-agent checkpoint blockade
Abstract Immune checkpoint inhibitors have demonstrated broad single-agent antitumor activity and a favorable safety profile that render them attractive agents to combine with other systemic anticancer therapies. Pancreatic cancer has been fairly resistant to monotherapy blockade of programmed cell...
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doaj-c053cfdb33884e4eb8430dd7526239dd2020-11-25T02:50:00ZengWileyClinical and Translational Medicine2001-13262018-10-017111610.1186/s40169-018-0210-9Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single-agent checkpoint blockadeJun Gong0Andrew Hendifar1Richard Tuli2Jeremy Chuang3May Cho4Vincent Chung5Daneng Li6Ravi Salgia7Department of Gastrointestinal Malignancies, Cedars-Sinai Medical CenterDepartment of Gastrointestinal Malignancies, Cedars-Sinai Medical CenterDepartment of Radiation Oncology, Cedars-Sinai Medical CenterDepartment of Internal Medicine, Harbor-UCLA Medical CenterDepartment of Internal Medicine, Division of Hematology and Oncology, UC Davis Comprehensive Cancer CenterDepartment of Medical Oncology, City of Hope National Medical CenterDepartment of Medical Oncology, City of Hope National Medical CenterMedical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer CenterAbstract Immune checkpoint inhibitors have demonstrated broad single-agent antitumor activity and a favorable safety profile that render them attractive agents to combine with other systemic anticancer therapies. Pancreatic cancer has been fairly resistant to monotherapy blockade of programmed cell death protein 1 receptor, programmed death ligand 1, and cytotoxic T-lymphocyte associated protein 4. However, there is a growing body of preclinical evidence to support the rational combination of checkpoint inhibitors and various systemic therapies in pancreatic cancer. Furthermore, early clinical evidence has begun to support the feasibility and efficacy of checkpoint inhibitor-based combination therapy in advanced pancreatic cancer. Despite accumulating preclinical and clinical data, there remains several questions as to the optimal dosing and timing of administration of respective agents, toxicity of combination strategies, and mechanisms by which immune resistance to single-agent checkpoint blockade are overcome. Further development of biomarkers is also important in the advancement of combination systemic therapies incorporating checkpoint blockade in pancreatic cancer. Results from an impressive number of ongoing prospective clinical trials are eagerly anticipated and will seek to validate the viability of combination immuno-oncology strategies in pancreatic cancer.http://link.springer.com/article/10.1186/s40169-018-0210-9Pancreatic cancerCheckpoint inhibitorCombination therapyImmuno-oncologyClinical trials |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jun Gong Andrew Hendifar Richard Tuli Jeremy Chuang May Cho Vincent Chung Daneng Li Ravi Salgia |
spellingShingle |
Jun Gong Andrew Hendifar Richard Tuli Jeremy Chuang May Cho Vincent Chung Daneng Li Ravi Salgia Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single-agent checkpoint blockade Clinical and Translational Medicine Pancreatic cancer Checkpoint inhibitor Combination therapy Immuno-oncology Clinical trials |
author_facet |
Jun Gong Andrew Hendifar Richard Tuli Jeremy Chuang May Cho Vincent Chung Daneng Li Ravi Salgia |
author_sort |
Jun Gong |
title |
Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single-agent checkpoint blockade |
title_short |
Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single-agent checkpoint blockade |
title_full |
Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single-agent checkpoint blockade |
title_fullStr |
Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single-agent checkpoint blockade |
title_full_unstemmed |
Combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single-agent checkpoint blockade |
title_sort |
combination systemic therapies with immune checkpoint inhibitors in pancreatic cancer: overcoming resistance to single-agent checkpoint blockade |
publisher |
Wiley |
series |
Clinical and Translational Medicine |
issn |
2001-1326 |
publishDate |
2018-10-01 |
description |
Abstract Immune checkpoint inhibitors have demonstrated broad single-agent antitumor activity and a favorable safety profile that render them attractive agents to combine with other systemic anticancer therapies. Pancreatic cancer has been fairly resistant to monotherapy blockade of programmed cell death protein 1 receptor, programmed death ligand 1, and cytotoxic T-lymphocyte associated protein 4. However, there is a growing body of preclinical evidence to support the rational combination of checkpoint inhibitors and various systemic therapies in pancreatic cancer. Furthermore, early clinical evidence has begun to support the feasibility and efficacy of checkpoint inhibitor-based combination therapy in advanced pancreatic cancer. Despite accumulating preclinical and clinical data, there remains several questions as to the optimal dosing and timing of administration of respective agents, toxicity of combination strategies, and mechanisms by which immune resistance to single-agent checkpoint blockade are overcome. Further development of biomarkers is also important in the advancement of combination systemic therapies incorporating checkpoint blockade in pancreatic cancer. Results from an impressive number of ongoing prospective clinical trials are eagerly anticipated and will seek to validate the viability of combination immuno-oncology strategies in pancreatic cancer. |
topic |
Pancreatic cancer Checkpoint inhibitor Combination therapy Immuno-oncology Clinical trials |
url |
http://link.springer.com/article/10.1186/s40169-018-0210-9 |
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