Optimal use of BTK inhibitors in Waldenström’s macroglobulinemia: combination or single drug approach? DOI Creative Commons
Eirini Solia, Efstathios Kastritis

Therapeutic Advances in Hematology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

Waldenström macroglobulinemia is an indolent B-cell lymphoma which although remains incurable, there are a lot of treatment options. Today, Bruton tyrosine kinase inhibitors have central role in the management disease either as monotherapy or combination with other regimens, due to their efficacy, ease administration, and safety profile. However, still active clinical investigation further increase efficacy improve Combinations based on BTK may offer advantages. Second- third-generation also evaluated combinations aiming depth response, overcome genetic factors associated poorer outcomes reduce toxicity duration therapy.

Language: Английский

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

Citations

16
Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies DOI Creative Commons
Xiaopeng Peng, Zhihao Hu,

Limei Zeng

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(2), P. 533 - 578

Published: Sept. 12, 2023

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over past few decades, significant progress has been made development targeted epigenetic modulators (e.g., inhibitors). However, inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack subtype selectivity, drug resistance. As result, design new degraders) such as PROTACs, molecular glue, hydrophobic tagging (HyT) degraders garnered attention from both academia pharmaceutical industry, numerous discovered decade. In this review, we aim to provide an in-depth illustration degrading strategies (2017–2023) targeting proteins for cancer therapy, focusing on rational design, pharmacodynamics, pharmacokinetics, status, crystal structure information these degraders. Importantly, also deep insights into potential challenges corresponding remedies approach development. Overall, hope review will offer better mechanistic understanding serve useful guide emerging epigenetic-targeting

Language: Английский

Citations

27
Lymph node metastasis and tumor-educated immune tolerance: Potential therapeutic targets against distant metastasis DOI Creative Commons
Jei‐Ming Peng, Yu‐Li Su

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 215, P. 115731 - 115731

Published: Aug. 2, 2023

Lymph node metastasis has been shown to positively associated with the prognosis of many cancers. However, in clinical treatment, lymphadenectomy is not always successful, suggesting that immune cells tumor and sentinel lymph nodes still play a pivotal role immunosuppression. Recent studies had tumors can tolerate through multiple strategies, including tumor-induced macrophage reprogramming, T inactivation, production B pathogenic antibodies activation regulatory promote colonization, growth, nodes. We reviewed bidirectional effect on anti-tumor or promotion cancer cell during metastasis, mechanisms by which malignant modify create more favorable environment for growth survival cells. Research treatment strategies focusing system potential targets were also be discussed.

Language: Английский

Citations

12
Progress of research on PD-1/PD-L1 in leukemia DOI Creative Commons

Huizhen Cao,

Tianyu Wu, Xue Zhou

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 26, 2023

Leukemia cells prevent immune system from clearing tumor by inducing the immunosuppression of bone marrow (BM) microenvironment. In recent years, further understanding BM microenvironment and landscape leukemia has resulted in introduction several immunotherapies, including checkpoint inhibitors, T-cell engager, antibody drug conjugates, cellular therapies clinical trials. Among them, programmed cell death protein 1 (PD-1)/programmed death-ligand (PD-L1) axis is a significant for controlling responses, PD-1 receptor on tumor-infiltrating T bound PD-L1 cells. Consequently, activation reactive inhibited their apoptosis promoted, preventing rejection thus resulting occurrence tolerance. The PD-1/PD-L1 serves as mechanism which evade surveillance, inhibitors have been approved treatment lymphomas varieties solid tumors. However, development drugs targeting remains clinical-trial stage. this review, we tally up basic research trials leukemia, well discuss relevant toxicity impacts other immunotherapies such hematopoietic stem transplantation, bi-specific chimeric antigen immunotherapy.

Language: Английский

Citations

12
Acalabrutinib in High‐Risk Chronic Lymphocytic Leukaemia Naïve Patients: An Italian Multicenter Retrospective Observational Real‐Life Experience DOI Creative Commons
Idanna Innocenti, Annamaria Tomasso, Diana Giannarelli

et al.

Hematological Oncology, Journal Year: 2025, Volume and Issue: 43(1)

Published: Jan. 1, 2025

Language: Английский

Citations

0
BTKi-induced cardiovascular toxicity in CLL: Risk mitigation and management strategies DOI
Sofija Kozarac, Vojin Vuković, Michael G. Fradley

et al.

Blood Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 101268 - 101268

Published: Jan. 1, 2025

Language: Английский

Citations

0
PROTAC technology for prostate cancer treatment DOI Creative Commons
Zhen Wang, Dingpeng Zhang, Hiroyuki Inuzuka

et al.

Acta Materia Medica, Journal Year: 2025, Volume and Issue: 4(1)

Published: Jan. 1, 2025

Prostate cancer (PrCa) is the most prevalent urogenital affecting men. PrCa marked by uncontrolled cellular growth that leads to abnormal enlargement of prostate gland. The metastatic spread primary cause mortality, causing cell dissemination distant sites, such as bones, pelvis, and various visceral organs. Key contributors progression include genetic mutations, elevated androgen receptor expression, gene amplification, rise splice variants. Although deprivation therapy remains mainstay for early-stage treatment, efficacy temporary because many cases advance castration-resistant (CRPC), presenting a significant therapeutic hurdle. This review explores key biomarkers latest strategies CRPC with particular focus on innovative proteolysis-targeting chimera (PROTAC) technology. approach offers novel means degrading target proteins we discuss how PROTAC holds potential effective combat resistance mechanisms in CRPC.

Language: Английский

Citations

0
The preclinical discovery and development of zanubrutinib for the treatment of chronic lymphocytic leukemia DOI

Tina Schleicher,

Melanie Cohen, Solomon A. Graf

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Introduction The history of treating chronic lymphocytic leukemia (CLL) inflected in 2014 with the Food and Drug Administration's (FDA) approval ibrutinib, first-in-class small molecule inhibitor Bruton's tyrosine kinase (BTK). Zanubrutinib is a 2nd generation covalent BTK developed manufactured by BeiGene.

Language: Английский

Citations

0
Comprehensive biomarker profiles in hematological malignancies: improving diagnosis, prognosis, and treatment DOI

Ali Golestan,

Mohammadrasul Zareinejad, Amin Ramezani

et al.

Biomarkers in Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Feb. 27, 2025

Hematological malignancies present substantial challenges in clinical practice due to their heterogeneity and complex biological profiles. In these diseases, biomarkers – measurable indicators of states are indispensable for diagnosis, prognosis, therapeutic decision-making. Emerging significantly improving outcomes hematological cancers by enhancing early detection, refining prognostic assessments, enabling personalized treatment approaches, optimizing overall patient management. This progress translates into better more effective strategies treat manage malignancies. The field biomarker discovery has developed from basic morphological cytogenetic markers advanced molecular techniques, including polymerase chain reaction (PCR) next-generation sequencing (NGS), which have enhanced diagnostic accuracy led the development targeted therapies. Additionally, recent advent technologies like mass spectrometry single-cell RNA enables comprehensive profiling reveals novel that were previously undetectable. Our aim this manuscript is provide a overview immunohematological biomarkers, applications, future directions field.

Language: Английский

Citations

0
Pirtobrutinib in Chinese patients with relapsed or refractory B‐cell malignancies: A single‐arm, open‐label, phase 2, multicenter trial DOI Creative Commons
Yanyan Liu,

Ningjing Lin,

Shuhua Yi

et al.

International Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract Pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi), demonstrated clinically meaningful antitumor responses in covalent BTKi pretreated mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) or small (SLL) the global phase 1/2 BRUIN study. In this multi‐center, open‐label, 2 trial, we investigated efficacy safety of pirtobrutinib Chinese patients with relapsed/refractory (R/R) MCL, CLL/SLL, other B‐cell malignancies. All received once daily continuous 28‐day cycles. The primary endpoint was overall response rate (ORR). Efficacy assessed MCL CLL/SLL prior treatment all enrolled who at least one dose pirtobrutinib. Among 35 BTKis (cBTKi) ORR 62.9% (95% CI: 44.9, 78.5), median duration (DOR) not reached, 12‐month DOR 59.7% 35.3, 77.5). 11 cBTKi 63.6% 30.8, 89.1), 83.3% 27.3, 97.5). most common adverse events population ( n = 87) were anemia (32.2%) neutrophil count decreased (31.0%). Grade ≥3 hemorrhage occurred 2.3% there no cases atrial fibrillation/flutter. Pirtobrutinib R/R preliminary activity generally well‐tolerated new signals observed.

Language: Английский

Citations

0