Indolent lymphoid malignancies are a heterogenous group of cancers deriving from B-, T- and NK-cells. Depending on the origin of malignant cells they have different clinical presentations and outcomes. Recently, the role of chemotherapy has been diminished by the growing evidence that novel therapies targeting molecular pathways arise as the new standard in many clinical situations in patients with B-cell indolent malignancies.
B-cell receptor (BCR) signaling is crucial in B-cell lymphomas as its activation stimulates transduction pathways which are essential for B-cell survival, as well as differentiation and proliferation by two crucial kinases – the Bruton's tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K). The BTK inhibitors (BTKi) like ibrutinib, acalabrutinib and zanubrutinib, as well as PI3K inhibitors (PI3Ki) like idelalisib, copanlisib and duvelisib, which are already approved by FDA/EMA for treatment for several non-Hodgkin B-cell lymphomas (NHL). Presently, there are many new BTKi and PI3Ki with better efficacy and/or safety profile are being assessed in different phases of clinical trials.
The spleen tyrosine kinase (SYK) is of high importance, for both BCR and T-cell receptor (TCR) signaling, and small molecule SYK inhibitors are extensively studied in lymphoid malignancies. In addition to the aforementioned kinases, the accumulating molecular data has identified several potential druggable signaling pathways crucial for lymphoma development i.e., NOTCH, NF-?B and JAK-STAT.
Epigenetic abnormalities, including DNA methylation and histone methylation aberrations beside kinase mediated pathways play a key role in development and progression of lymphomas. Therefore, targeted drugs related to epigenetic modifications are an important subject of research in different lymphoid malignancies. The EZH2 inhibitor, tazemetostat, is approved for use in relapsed/refractory follicular lymphoma patients, while others like TET2 or IDH2 inhibitors are currently in the early phases of clinical development.
Shifting the balance towards apoptosis by targeting the antiapoptotic BCL-2 protein with venetoclax is a widely used strategy in the treatment of chronic lymphocytic leukemia. Considering the high clinical efficacy of venetoclax in chronic lymphocytic leukemia, its different combinations are also studied in the other indolent lymphoid malignancies and novel BCL2 inhibitors are currently evaluated in early stages clinical trials.
In this collection we would like to include manuscripts of both original research and review articles on the novel targeted agents under preclinical and clinical development with the potential to be introduced in the treatment of indolent lymphoid malignancies.
Important Note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
Indolent lymphoid malignancies are a heterogenous group of cancers deriving from B-, T- and NK-cells. Depending on the origin of malignant cells they have different clinical presentations and outcomes. Recently, the role of chemotherapy has been diminished by the growing evidence that novel therapies targeting molecular pathways arise as the new standard in many clinical situations in patients with B-cell indolent malignancies.
B-cell receptor (BCR) signaling is crucial in B-cell lymphomas as its activation stimulates transduction pathways which are essential for B-cell survival, as well as differentiation and proliferation by two crucial kinases – the Bruton's tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K). The BTK inhibitors (BTKi) like ibrutinib, acalabrutinib and zanubrutinib, as well as PI3K inhibitors (PI3Ki) like idelalisib, copanlisib and duvelisib, which are already approved by FDA/EMA for treatment for several non-Hodgkin B-cell lymphomas (NHL). Presently, there are many new BTKi and PI3Ki with better efficacy and/or safety profile are being assessed in different phases of clinical trials.
The spleen tyrosine kinase (SYK) is of high importance, for both BCR and T-cell receptor (TCR) signaling, and small molecule SYK inhibitors are extensively studied in lymphoid malignancies. In addition to the aforementioned kinases, the accumulating molecular data has identified several potential druggable signaling pathways crucial for lymphoma development i.e., NOTCH, NF-?B and JAK-STAT.
Epigenetic abnormalities, including DNA methylation and histone methylation aberrations beside kinase mediated pathways play a key role in development and progression of lymphomas. Therefore, targeted drugs related to epigenetic modifications are an important subject of research in different lymphoid malignancies. The EZH2 inhibitor, tazemetostat, is approved for use in relapsed/refractory follicular lymphoma patients, while others like TET2 or IDH2 inhibitors are currently in the early phases of clinical development.
Shifting the balance towards apoptosis by targeting the antiapoptotic BCL-2 protein with venetoclax is a widely used strategy in the treatment of chronic lymphocytic leukemia. Considering the high clinical efficacy of venetoclax in chronic lymphocytic leukemia, its different combinations are also studied in the other indolent lymphoid malignancies and novel BCL2 inhibitors are currently evaluated in early stages clinical trials.
In this collection we would like to include manuscripts of both original research and review articles on the novel targeted agents under preclinical and clinical development with the potential to be introduced in the treatment of indolent lymphoid malignancies.
Important Note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
