The role of PI3K inhibition in lymphoid malignancies Review
| Authors: | von Keudell, G.; Moskowitz, A. J. |
| Review Title: | The role of PI3K inhibition in lymphoid malignancies |
| Abstract: | Purpose of Review: The outcome of patients with lymphoid malignancies has markedly improved in recent years which is likely due to a combination of advances in supportive care, and therapeutic options. In this article, we will provide an overview over the role PI3-kinase signalling, one of the most important dysregulated pathways in cancer, and its successful inhibition in lymphoma. Recent Findings: PI3-kinase inhibitors have shown remarkable activity in an increasing subset of patients with non-Hodgkin lymphomas. The first drug to be approved was idelalisib for patients with relapsed/refractory follicular lymphoma and CLL/SLL as monotherapy, or in combination with rituximab, respectively. After an initial setback related to increased toxicity including deaths observed in several upfront studies, there has been a resurgence in interest in this pathway following the promising efficacy of second-generation PI3K inhibitors including in patients with T cell lymphomas. Summary: PI3K inhibition continues to be an invaluable tool in the therapy of patients with lymphoid malignancies if managed cautiously. Preclinical models are helpful in predicting possible side effects and identifying new lymphoma subtypes that may be susceptible to this class of agents. The future will likely involve rationally designed combinatorial approaches to deepen the response rate and prevent the emergence of resistance. © 2019, Springer Science+Business Media, LLC, part of Springer Nature. |
| Keywords: | signal transduction; protein expression; protein phosphorylation; treatment response; gene mutation; overall survival; lenalidomide; neutropenia; review; cancer recurrence; diarrhea; rituximab; tumor associated leukocyte; gene targeting; progression free survival; apoptosis; bortezomib; enzyme inhibition; anemia; thrombocytopenia; macrophage inflammatory protein 1beta; antineoplastic activity; enzyme activation; phosphatidylinositol 3 kinase; coughing; pneumonia; b cell lymphoma; t cell lymphoma; activation induced cytidine deaminase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; lymphoma; drug toxicity; glucose homeostasis; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; follicular lymphoma; marginal zone lymphoma; cytomegalovirus infection; isoprotein; infection sensitivity; cll; cd79a antigen; phosphatidylinositol 3 kinase inhibitor; stromal cell derived factor 1; tumor microenvironment; transcription factor foxo; clinical trial (topic); isoenzyme; hypertransaminasemia; b lymphocyte receptor; ofatumumab; lymphocytosis; akt signaling; macrophage inflammatory protein 1alpha; pi3-kinase; idelalisib; buparlisib; human; copanlisib; caspase 11; duvelisib; cxcl13 chemokine; b cell receptor; itacitinib; umbralisib; cd79b antigen; dezapelisib; entospletinib; fimepinostat |
| Journal Title: | Current Hematologic Malignancy Reports |
| Volume: | 14 |
| Issue: | 5 |
| ISSN: | 1558-8211 |
| Publisher: | Springer |
| Date Published: | 2019-10-01 |
| Start Page: | 405 |
| End Page: | 413 |
| Language: | English |
| DOI: | 10.1007/s11899-019-00540-w |
| PUBMED: | 31359259 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Export Date: 2 December 2019 -- Source: Scopus |
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