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We herein review some of the major patterns of resistance and lessons learned from the use of earlier targeted therapies in two genotype-driven solid tumors.
Targeted agents have rapidly expanded in the field of oncology over the past 2 decades. The breakthroughs achieved by these agents have been, however, hindered by the inevitable development of drug resistance. Intrinsic or acquired mechanisms of resistance eventually lead to treatment tolerance and tumoral plasticity with phenotypic switch and evasion of the original targeted pathway. Failures in such therapies also result from poor selectivity of the target, drug delivery, and unaffordable costs.
Based on above findings, collaborative efforts are advancing at the molecular level to design better drugs or combinatorial strategies and to develop more sensitive assays to monitor responses and the emergence of resistance.
Based on above findings, collaborative efforts are advancing at the molecular level to design better drugs or combinatorial strategies and to develop more sensitive assays to monitor responses and the emergence of resistance.
PARP inhibitors have transformed the management of BRCA mutant (BRCA) high-grade serous and endometroid ovarian cancer (HGOC). However, it is clear that the benefit can be extended beyond this subgroup, particularly to those cancers with homologous recombination repair deficiency (HRD). We review emerging molecular and clinical data to support the use of PARP inhibitors in HRD HGOC and discuss the advantages and disadvantages of different HRD assays.
AP20187 cost support the use of PARP inhibitor maintenance therapy beyond those patients with BRCA in the first-line and platinum-sensitive relapse setting. Many of these studies included HRD testing and it is clear, regardless of the assay used, that an incremental reduction in benefit is observed from BRCA tumours to HRD to homologous recombination proficient tumours. However, although currently available HRD assays predict the magnitude of benefit from PARP inhibitors, they consistently fail to identify a subgroup of patients who do not benefit.
Clinical data support the use of PARP inhibitor maintenance therapy beyond BRCA patients. Current HRD tests lack negative predictive value and more research is required to develop a composite HRD assay that provides a dynamic readout of HRD status.
Clinical data support the use of PARP inhibitor maintenance therapy beyond BRCA patients. #link# Current HRD tests lack negative predictive value and more research is required to develop a composite HRD assay that provides a dynamic readout of HRD status.
Chimeric antigen receptor (CAR) T-cell therapy is an innovative form of adoptive cellular immunotherapy targeting CD19 in its most advanced form. Up to 30% of infused patients achieve long-term survival, meaning that 70% of patients still fail to respond or relapse after therapy. This review will address the unresolved issues relating to responders' characterization, relapse prediction, and prevention, CAR T-cell construct optimization, rational combination with other therapies and treatment toxicity, focusing on the management of relapsed/refractory lymphoma patients.
Many new antigenic targets are currently investigated and raise the hope of broader successes. However, literature data report that treatment failure is not only related to CAR T construct and infusion but is also due to hostile tumor microenvironment and poor interaction with the host effector cells. Further research should not only target CAR T structure, toxicity and associated therapies, but also tumor-related and host-related microenvideeper understanding of CAR T-cell therapy failure in individuals will help personalize CAR T-cell therapy in the future.
A number of clinical trials are currently testing chimeric antigen receptor (CAR) and T cell receptor (TCR) engineered T cells for the treatment of haematologic malignancies and selected solid tumours, and CD19-CAR-T cells have produced impressive clinical responses in B-cell malignancies. Here, we summarize the current state of the field, highlighting the key aspects required for the optimal application of CAR and TCR-engineered T cells for cancer immunotherapy.
Toxicities, treatment failure and disease recurrence have been observed at different rates and kinetics. Several strategies have been designed to overcome these hurdles the identification and combination of known and new antigens, together with the combination of immunotherapeutic and classical approaches may overcome cancer immune evasion. New protocols for genetic modification and T cell culture may improve the overall fitness of cellular products and their resistance to hostile tumour immunomodulatory signals. Finally, the schedules of T cell administration and toxicity management have been adapted to improve the safety of this transformative therapeutic approach.
In order to develop effective adoptive T cell treatments for cancer, therapeutic optimization of engineered CAR and TCR T cells is crucial, by simultaneously focusing on intrinsic and extrinsic factors. This review focuses on the innovative approaches designed and tested to overcome the hurdles encountered so far in the clinical practice, with new excitement on novel laboratory insights and ongoing clinical investigations.
In order to develop effective adoptive T cell treatments for cancer, therapeutic optimization of engineered CAR and TCR T cells is crucial, by simultaneously focusing on intrinsic and extrinsic factors. This review focuses on the innovative approaches designed and tested to overcome the hurdles encountered so far in the clinical practice, with new excitement on novel laboratory insights and ongoing clinical investigations.
Sodium restriction is difficult for most individuals with hypertension. Intention to limit sodium intake predicts behavior. Information on the determinants of intention to restrict sodium intake is limited.
The aims of this study were to identify (1) determinants of intention to restrict high-sodium food intake and (2) sources of sodium consumed by patients with hypertension in Indonesia.
A cross-sectional study was conducted among adult patients with hypertension (n = 206) attending cardiac clinics. A researcher-developed and tested, self-administered questionnaire that included questions about sodium restriction and a high-sodium food inventory was distributed. The quantile regression method was used to identify determinants of intention to restrict dietary sodium.
The mean age of the patients with hypertension was 59 ± 10 years, and more than three-fourths were obese (n = 162, 78%). The determinants of intention to limit sodium intake included gender (β = 0.737, P = .036), attitude (β = -0.141, P = .
Read More: https://www.selleckchem.com/products/ap20187.html
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