Targeting the JAK/STAT Pathway in T Cell Lymphoproliferative Disorders

AbstractPurpose of ReviewT cell lymphoproliferative disorders represent a diverse group of hematologic malignancies with poor prognosis underscoring the need for novel therapeutic approaches. Disruption of the JAK/STAT signaling pathway has been described in this group of blood cancers and may represent an approach for targeted therapy. Here, we summarize the current data describing the disruptions of JAK/STAT signaling in T cell malignancies and focus on the existing evidence for exploitation of this pathway with targeted therapies.Recent FindingsTo date, preclinical studies have demonstrated the efficacy of JAK/STAT inhibition in the treatment of several T cell lymphoproliferative disorders. More recently, several early clinical trials have demonstrated promising results utilizing this approach as well. The benefit of the combination of JAK/STAT-targeted therapies along with immunotherapy and other molecularly targeted therapies is also discussed.SummaryThere is substantial evidence that targeting the JAK/STAT pathway in T cell lymphoproliferative disorders could be of clinical benefit. There are several early clinical trials showing promise and many ongoing trials investigating the optimal utility of agents that inhibit this signaling pathway. In addition, targeting this pathway may provide a platform for further rational combination therapies.
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research

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The objective response rate (ORR) was 30% (10/33), including three complete responses (CR) (9.1%) and seven partial responses (PR) (21.2%) and a disease control rate (DCR = CR + PR + SD) of 66.7% (22 of 33). The most common adverse reactions, blistering, subcutaneous fat induration, local heat-related pain, vomiting and sinus tachycardia, were observed in association with HT. IL-2, IL-4, TNF-α, and IFN-γ levels in peripheral blood were significantly increased among the clinical responders (p 
Source: International Journal of Hyperthermia - Category: Internal Medicine Tags: Int J Hyperthermia Source Type: research
Conclusions: These studies suggest that in addition to its role as a palliative therapeutic modality, RFA may have clinical potential as an immune-adjuvant therapy by augmenting the efficacy of adoptive T cell therapy. PMID: 31795828 [PubMed - in process]
Source: International Journal of Hyperthermia - Category: Internal Medicine Tags: Int J Hyperthermia Source Type: research
Authors: Hurwitz MD Abstract Hyperthermia holds great promise to advance immunotherapy in the treatment of cancer. Multiple trials have demonstrated benefit with the addition of hyperthermia to radiation or chemotherapy in the treatment of wide-ranging malignancies. Similarly, pre-clinical studies have demonstrated the ability of hyperthermia to enhance each of the 8 steps in the cancer-immunotherapy cycle including stimulation of tumor-specific immunity. While there has been an extensive recent focus on augmenting immunotherapy with radiation, surprisingly to date, there have been no clinical trials assessing the ...
Source: International Journal of Hyperthermia - Category: Internal Medicine Tags: Int J Hyperthermia Source Type: research
Condition:   Head and Neck Neoplasms Intervention:   Drug: Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA] Sponsor:   Henry Ford Health System Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Recurrent Cervical Carcinoma;   Persistent Advanced Cervical Carcinoma;   Chemotherapy;   Anti-PD-1 Antibody;   Immunotherapy Intervention:   Drug: A combination of anti-PD-1 antibody camrelizumab and albumin-bound paclitaxel Sponsor:   Lei Li Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusion The use of Hopkins criteria for posttherapy assessment in patients with lung cancer represents an easy and reproducible method with substantial to almost perfect interobserver agreement and high positive predictive value and accuracy; moreover, it is easily understood by referring physicians. Additionally, there was no significant difference when applying a semi-quantitative measure to the same five-point score.
Source: Nuclear Medicine Communications - Category: Nuclear Medicine Tags: Original Articles Source Type: research
Authors: Han RH, Dunn GP, Chheda MG, Kim AH Abstract Metastases from melanoma, lung and breast cancer are among the most common causes of intracranial malignancy. Standard of care for brain metastases include a combination of surgical resection, stereotactic radiosurgery, and whole-brain radiation. However, evidence continues to accumulate regarding the efficacy of molecularly-targeted systemic treatments and immunotherapy. For non-small cell lung cancer (NSCLC), numerous clinical trials have demonstrated intracranial activity for inhibitors of EGFR and ALK. Patients with melanoma brain metastases may benefit from ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Conclusions: The selective inhibition of RIPK1 with small molecule inhibitors can be used as a pharmaceutical tool to transiently mask TNF activity and improve the therapeutic window of TNF-based biopharmaceuticals. Similar approaches may be applicable to other pro-inflammatory cytokines. PMID: 31803362 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: Ettinger DS, Wood DE, Aggarwal C, Aisner DL, Akerley W, Bauman JR, Bharat A, Bruno DS, Chang JY, Chirieac LR, D'Amico TA, Dilling TJ, Dobelbower M, Gettinger S, Govindan R, Gubens MA, Hennon M, Horn L, Lackner RP, Lanuti M, Leal TA, Lin J, Loo BW, Martins RG, Otterson GA, Patel SP, Reckamp KL, Riely GJ, Schild SE, Shapiro TA, Stevenson J, Swanson SJ, Tauer KW, Yang SC, Gregory K, OCN, Hughes M Abstract The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates in immunotherapy. For the 2020 update, all of th...
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
Authors: Park S, Kar N, Cheong JH, Hwang TH Abstract Accurate identification of pathways associated with cancer phenotypes (e.g., cancer subtypes and treatment outcomes) could lead to discovering reliable prognostic and/or predictive biomarkers for better patients stratification and treatment guidance. In our previous work, we have shown that non-negative matrix tri-factorization (NMTF) can be successfully applied to identify pathways associated with specific cancer types or disease classes as a prognostic and predictive biomarker. However, one key limitation of non-negative factorization methods, including various...
Source: Pacific Symposium on Biocomputing - Category: Bioinformatics Tags: Pac Symp Biocomput Source Type: research
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