Abstract Cancer therapies will increasingly be utilized in combination to treat advanced malignancies so as to increase their long-term efficacy in a greater proportion of patients. In particular, much attention has focused on developing targeted therapies that inhibit the PI3K-AKT-mTOR signaling network which is dysregulated in many cancer types. In addition, there is now a growing appreciation that targeting of these pathways can impact not only on cancer cells, but also host immunity. The clinical success of cancer immunotherapies targeting T-cell immune checkpoint receptors PD-1/PD-L1 has demonstrated the importance of immunoevasion as a hallmark of cancer. In this review, we discuss how PI3K-AKT-mTOR inhibitors target cancer cell biology, attenuate immune cell effector function and modulate the tumor microenvironment. We next discuss how the immunomodulatory potential of these inhibitors can be exploited through rational combinations with immunotherapies and targeted therapies.
PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux / O'Donnell, Jake S.; Massi, Daniela; Teng, Michele W.L.; Mandala, Mario*. - In: SEMINARS IN CANCER BIOLOGY. - ISSN 1044-579X. - ELETTRONICO. - 48:(2018), pp. 91-103. [10.1016/j.semcancer.2017.04.015]
PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux
Massi, Daniela;
2018
Abstract
Abstract Cancer therapies will increasingly be utilized in combination to treat advanced malignancies so as to increase their long-term efficacy in a greater proportion of patients. In particular, much attention has focused on developing targeted therapies that inhibit the PI3K-AKT-mTOR signaling network which is dysregulated in many cancer types. In addition, there is now a growing appreciation that targeting of these pathways can impact not only on cancer cells, but also host immunity. The clinical success of cancer immunotherapies targeting T-cell immune checkpoint receptors PD-1/PD-L1 has demonstrated the importance of immunoevasion as a hallmark of cancer. In this review, we discuss how PI3K-AKT-mTOR inhibitors target cancer cell biology, attenuate immune cell effector function and modulate the tumor microenvironment. We next discuss how the immunomodulatory potential of these inhibitors can be exploited through rational combinations with immunotherapies and targeted therapies.File | Dimensione | Formato | |
---|---|---|---|
2158-1129680_postprint.pdf
Open Access dal 01/01/2020
Tipologia:
Versione finale referata (Postprint, Accepted manuscript)
Licenza:
Creative commons
Dimensione
2.74 MB
Formato
Adobe PDF
|
2.74 MB | Adobe PDF | |
1-s2.0-S1044579X1730113X-main.pdf
Accesso chiuso
Tipologia:
Pdf editoriale (Version of record)
Licenza:
Tutti i diritti riservati
Dimensione
962.12 kB
Formato
Adobe PDF
|
962.12 kB | Adobe PDF | Richiedi una copia |
I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.