Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?

Aydin, Ebru; Faehling, Sebastian; Saleh, Mariam; Cid, Laura Llaó; Seiffert, Martina; Roessner, Philipp M.

doi:10.3389/fimmu.2020.595818

Cited by 15 publications

(30 citation statements)

References 173 publications

(343 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, inhibitory targeting of macrophage signaling pathways might be associated with better prognosis of cancer patients. In this context, the Phosphatidylinositol 3-kinase (PI3K) signaling pathway, which is of vital importance in the regulation of cell survival, but also in the malignant transformation of cells, was also involved in the pro-tumoural activity of macrophages, as reported in several cancers such as human head and neck squamous cell carcinoma (HNSCC) [ 256 ] and human chronic lymphocytic leukemia (CLL) [ 257 ]. PI3Kγ regulates NF-κB and CCAAT/enhancer-binding protein-β (C/EBPβ) during macrophage polarisation, thereby regulating macrophage immune responses.…”

Section: Dual Effect Of Immune Cells In Cancermentioning

confidence: 99%

Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

Peña-Romero

Orenes‐Piñero

2022

Cancers

View full text Add to dashboard Cite

Our body is constantly exposed to pathogens or external threats, but with the immune response that our body can develop, we can fight off and defeat possible attacks or infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as the existence of a tumour also cause our immune system (IS) to be put on alert. Indeed, the link between immunology and cancer is evident these days, with IS being used as one of the important targets for treating cancer. Our IS is able to eliminate those abnormal or damaged cells found in our body, preventing the uncontrolled proliferation of tumour cells that can lead to cancer. However, in several cases, tumour cells can escape from the IS. It has been observed that immune cells, the extracellular matrix, blood vessels, fat cells and various molecules could support tumour growth and development. Thus, the developing tumour receives structural support, irrigation and energy, among other resources, making its survival and progression possible. All these components that accompany and help the tumour to survive and to grow are called the tumour microenvironment (TME). Given the importance of its presence in the tumour development process, this review will focus on one of the components of the TME: immune cells. Immune cells can support anti-tumour immune response protecting us against tumour cells; nevertheless, they can also behave as pro-tumoural cells, thus promoting tumour progression and survival. In this review, the anti-tumour and pro-tumour immunity of several immune cells will be discussed. In addition, the TME influence on this dual effect will be also analysed.

show abstract

Section: Dual Effect Of Immune Cells In Cancermentioning

confidence: 99%

Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

Peña-Romero

Orenes‐Piñero

2022

Cancers

View full text Add to dashboard Cite

show abstract

“…It is tempting to speculate, therefore, that SMER28 might specifically interfere with a cellular kinase involved in CLIP-170 phosphorylation 12 , 13 , 82 , and induces autophagy at the level of or downstream of PI3Ks 83 . PI3Ks are important pharmacologic targets, and drugs modulating their activities are under intense investigation 84 – 86 . Of note, AMPK is a key energy sensor and regulates cellular metabolism and autophagy induction 87 .…”

Section: Discussionmentioning

confidence: 99%

The autophagy inducer SMER28 attenuates microtubule dynamics mediating neuroprotection

Kirchenwitz

Stahnke

Grunau

et al. 2022

Sci Rep

View full text Add to dashboard Cite

SMER28 originated from a screen for small molecules that act as modulators of autophagy. SMER28 enhanced the clearance of autophagic substrates such as mutant huntingtin, which was additive to rapamycin-induced autophagy. Thus, SMER28 was established as a positive regulator of autophagy acting independently of the mTOR pathway, increasing autophagosome biosynthesis and attenuating mutant huntingtin-fragment toxicity in cellular- and fruit fly disease models, suggesting therapeutic potential. Despite many previous studies, molecular mechanisms mediating SMER28 activities and its direct targets have remained elusive. Here we analyzed the effects of SMER28 on cells and found that aside from autophagy induction, it significantly stabilizes microtubules and decelerates microtubule dynamics. Moreover, we report that SMER28 displays neurotrophic and neuroprotective effects at the cellular level by inducing neurite outgrowth and protecting from excitotoxin-induced axon degeneration. Finally, we compare the effects of SMER28 with other autophagy-inducing or microtubule-stabilizing drugs: whereas SMER28 and rapamycin both induce autophagy, the latter does not stabilize microtubules, and whereas both SMER28 and epothilone B stabilize microtubules, epothilone B does not stimulate autophagy. Thus, the effect of SMER28 on cells in general and neurons in particular is based on its unique spectrum of bioactivities distinct from other known microtubule-stabilizing or autophagy-inducing drugs.

show abstract

“…NFAT : nuclear factor of activated T-cells. Created with based on information in [ 37 , 38 , 50 , 51 ].…”

Section: Figurementioning

confidence: 99%

FDA-Approved Drugs for Hematological Malignancies—The Last Decade Review

Sochacka-Ćwikła

Mączyński

Regiec

2021

Cancers

View full text Add to dashboard Cite

Hematological malignancies, also referred to as blood cancers, are a group of diseases involving abnormal cell growth and persisting in the blood, lymph nodes, or bone marrow. The development of new targeted therapies including small molecule inhibitors, monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, recombinant immunotoxins, and, finally, Chimeric Antigen Receptor T (CAR-T) cells has improved the clinical outcomes for blood cancers. In this review, we summarized 52 drugs that were divided into small molecule and macromolecule agents, approved by the Food and Drug Administration (FDA) in the period between 2011 and 2021 for the treatment of hematological malignancies. Forty of them have also been approved by the European Medicines Agency (EMA). We analyzed the FDA-approved drugs by investigating both their structures and mechanisms of action. It should be emphasized that the number of targeted drugs was significantly higher (46 drugs) than chemotherapy agents (6 drugs). We highlight recent advances in the design of drugs that are used to treat hematological malignancies, which make them more effective and less toxic.

show abstract

Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?

Cited by 15 publications

References 173 publications

Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

The autophagy inducer SMER28 attenuates microtubule dynamics mediating neuroprotection

FDA-Approved Drugs for Hematological Malignancies—The Last Decade Review

Contact Info

Product

Resources

About