Abstract
Introduction: The broad use of immunotherapy is revolutionizing the treatment paradigms of many solid tumors. Although chemotherapy remains the treatment backbone for advanced gastric cancer, improvements in its molecular characterization and progresses in understanding its underpinning biology have supported clinical development of novel immunotherapies. However, the results of recent trials testing these new agents raise the question on how to identify the patients that could greatly benefit. Areas covered: This article summarizes the current understanding on the biology and the mechanisms underlying different clinical features of gastric cancers. Particularly, after a comprehensive literature search, we speculate whether specific molecular subsets of patients could derive more benefit from immunotherapy. Expert commentary: Most cancers may evade the immune response, which is normally regulated by a delicate balance between activating and inhibitory signals. For example, both CTLA-4 and PD-1, once linked to PD-L1/2, may inhibit T-cell signaling. The use of agent to harness the power of the immune system appears to be the ultimate frontier in gastric cancer treatment. While anti-CTLA-4 antibodies are minimally active, there is growing evidence for the efficacy of PD1/-L1 inhibitors. The search of predictive factors for immunotherapy will provide key hints towards the optimal use of these agents.
| Original language | English |
|---|---|
| Pages (from-to) | 609-619 |
| Number of pages | 11 |
| Journal | Expert Review of Clinical Pharmacology |
| Volume | 10 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 3 2017 |
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Keywords
- Gastric cancer
- immunotherapy
- molecular classification
- PD-L1
- PD-L2
ASJC Scopus subject areas
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology (medical)
Cite this
Immunotherapy for gastric cancers : emerging role and future perspectives. / Bonotto, Marta; Garattini, Silvio Ken; Basile, Debora; Ongaro, Elena; Fanotto, Valentina; Cattaneo, Monica; Cortiula, Francesco; Iacono, Donatella; Cardellino, Giovanni Gerardo; Pella, Nicoletta; Fasola, Gianpiero; Antonuzzo, Lorenzo; Silvestris, Nicola; Aprile, Giuseppe.
In: Expert Review of Clinical Pharmacology, Vol. 10, No. 6, 03.06.2017, p. 609-619.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Immunotherapy for gastric cancers
T2 - emerging role and future perspectives
AU - Bonotto, Marta
AU - Garattini, Silvio Ken
AU - Basile, Debora
AU - Ongaro, Elena
AU - Fanotto, Valentina
AU - Cattaneo, Monica
AU - Cortiula, Francesco
AU - Iacono, Donatella
AU - Cardellino, Giovanni Gerardo
AU - Pella, Nicoletta
AU - Fasola, Gianpiero
AU - Antonuzzo, Lorenzo
AU - Silvestris, Nicola
AU - Aprile, Giuseppe
PY - 2017/6/3
Y1 - 2017/6/3
N2 - Introduction: The broad use of immunotherapy is revolutionizing the treatment paradigms of many solid tumors. Although chemotherapy remains the treatment backbone for advanced gastric cancer, improvements in its molecular characterization and progresses in understanding its underpinning biology have supported clinical development of novel immunotherapies. However, the results of recent trials testing these new agents raise the question on how to identify the patients that could greatly benefit. Areas covered: This article summarizes the current understanding on the biology and the mechanisms underlying different clinical features of gastric cancers. Particularly, after a comprehensive literature search, we speculate whether specific molecular subsets of patients could derive more benefit from immunotherapy. Expert commentary: Most cancers may evade the immune response, which is normally regulated by a delicate balance between activating and inhibitory signals. For example, both CTLA-4 and PD-1, once linked to PD-L1/2, may inhibit T-cell signaling. The use of agent to harness the power of the immune system appears to be the ultimate frontier in gastric cancer treatment. While anti-CTLA-4 antibodies are minimally active, there is growing evidence for the efficacy of PD1/-L1 inhibitors. The search of predictive factors for immunotherapy will provide key hints towards the optimal use of these agents.
AB - Introduction: The broad use of immunotherapy is revolutionizing the treatment paradigms of many solid tumors. Although chemotherapy remains the treatment backbone for advanced gastric cancer, improvements in its molecular characterization and progresses in understanding its underpinning biology have supported clinical development of novel immunotherapies. However, the results of recent trials testing these new agents raise the question on how to identify the patients that could greatly benefit. Areas covered: This article summarizes the current understanding on the biology and the mechanisms underlying different clinical features of gastric cancers. Particularly, after a comprehensive literature search, we speculate whether specific molecular subsets of patients could derive more benefit from immunotherapy. Expert commentary: Most cancers may evade the immune response, which is normally regulated by a delicate balance between activating and inhibitory signals. For example, both CTLA-4 and PD-1, once linked to PD-L1/2, may inhibit T-cell signaling. The use of agent to harness the power of the immune system appears to be the ultimate frontier in gastric cancer treatment. While anti-CTLA-4 antibodies are minimally active, there is growing evidence for the efficacy of PD1/-L1 inhibitors. The search of predictive factors for immunotherapy will provide key hints towards the optimal use of these agents.
KW - Gastric cancer
KW - immunotherapy
KW - molecular classification
KW - PD-L1
KW - PD-L2
UR - http://www.scopus.com/inward/record.url?scp=85019610649&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019610649&partnerID=8YFLogxK
U2 - 10.1080/17512433.2017.1313113
DO - 10.1080/17512433.2017.1313113
M3 - Review article
VL - 10
SP - 609
EP - 619
JO - Expert Review of Clinical Pharmacology
JF - Expert Review of Clinical Pharmacology
SN - 1751-2433
IS - 6
ER -