How to target PI3Ks 3 classes in cancer?

PI3K,

cell signaling,

Combi/hydrides-molecules,

combination therapeutics,

Cancer,

Benoît Thibault, équipe SigDyn – Signalisation cellulaire intégrée et isoformes de PI3K

PI3Ks are a family of 3 classes of enzymes that are crucial for the life of the cell. They are often deregulated in cancer. In this review, we summarise the work of the last 5 years on the role of PI3Ks in cancer as well as the advances of drugs targeting these enzymes in preclinical models. The dependence of tumours on different types of class I PI3K is governed by possible genetic mutations or the tumour context (inflammation, etc.). Knowledge about class II and III PI3Ks in cancer is still too limited but reveals a dependence with class I PI3Ks on similar mechanisms responsible for tumour growth. The future of anti-cancer therapies targeting PI3Ks lies in a better understanding of these enzymes and simultaneous targeting of several classes of PI3Ks with innovative drugs.

This literature review aims to compile recent data on the role of different classes of PI3Ks in cancer and to propose innovative therapeutic strategies to optimise the targeting of PI3Ks in the clinic.

This work highlights the gaps in knowledge about PI3Ks. In particular, the role of class II and III PI3Ks in cancer is poorly understood. Similarly, their interactions with class I PI3Ks are not studied, although they probably constitute a key point in the resistance of tumours to PI3K inhibitors. With this review, we hope to guide teams working in the field of PI3Ks on the key points to study on these enzymes in the future.

The future of anti-PI3K therapies in cancer requires to target simultaneously several PI3K classes

Discover the published article

Cancers (Basel). 2023 Jan 27;15(3):784.doi: 10.3390/cancers15030784.
Targeting Class I-II-III PI3Ks in Cancer Therapy: Recent Advances in Tumor Biology and Preclinical Research
Benoît Thibault, Fernanda Ramos-Delgado, Julie Guillermet-Guibert

Collaborations and acknowledgements

We would like to thank the following for their support of our research

ANR JCJC Radiance
Europe (MSCA-ITN/ETN PhD-PI3K)
IUCT-O/ICR translational research programme
Regional League Against Cancer
ARC Foundation
ANR (Toucan), laboratory of excellence

Centre de Recherches en Cancérologie de Toulouse

Toulouse Cancer Research Center (Oncopole)

Toulouse - FR

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