Giredestrant for Estrogen Receptor–Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study DOI Creative Commons
Miguel Martín, Elgene Lim, Mariana Chávez‐MacGregor

и другие.

Journal of Clinical Oncology, Год журнала: 2024, Номер 42(18), С. 2149 - 2160

Опубликована: Март 27, 2024

PURPOSE To compare giredestrant and physician's choice of endocrine monotherapy (PCET) for estrogen receptor–positive, HER2-negative, advanced breast cancer (BC) in the phase II acelERA BC study (ClinicalTrials.gov identifier: NCT04576455 ). METHODS Post-/pre-/perimenopausal women, or men, age 18 years older with measurable disease/evaluable bone lesions, whose disease progressed after 1-2 lines systemic therapy (≤1 targeted, ≤1 chemotherapy regimen, prior fulvestrant allowed) were randomly assigned 1:1 to (30 mg oral once daily) fulvestrant/aromatase inhibitor per local guidelines (+luteinizing hormone–releasing hormone agonist pre-/perimenopausal men) until progression/unacceptable toxicity. Stratification was by visceral versus nonvisceral disease, cyclin-dependent kinase 4/6 inhibitor, fulvestrant. The primary end point investigator-assessed progression-free survival (INV-PFS). RESULTS At clinical cutoff (February 18, 2022; median follow-up: 7.9 months; N = 303), INV-PFS hazard ratio (HR) 0.81 (95% CI, 0.60 1.10; P .1757). In prespecified secondary analysis ESR1 mutation (m) status circulating tumor DNA–evaluable patients (n 232), HR a detectable ESR1m 90) 0.35 1.03) 0.88 0.54 1.42) no detected 142). Related grade 3-4 adverse events (AEs), serious AEs, discontinuations due AEs balanced across arms. CONCLUSION Although did not reach statistical significance its point, there consistent treatment effect most key subgroups trend toward favorable benefit among ESR1-mutated tumors. Giredestrant well tolerated, safety profile comparable PCET known risks. Overall, these data support continued investigation other studies.

Язык: Английский

Breast cancer DOI
Sibylle Loibl, Philip Poortmans, Monica Morrow

и другие.

The Lancet, Год журнала: 2021, Номер 397(10286), С. 1750 - 1769

Опубликована: Апрель 2, 2021

Язык: Английский

Процитировано

1164
The lingering mysteries of metastatic recurrence in breast cancer DOI Creative Commons
Alessandra I. Riggio, Katherine E. Varley, Alana L. Welm

и другие.

British Journal of Cancer, Год журнала: 2020, Номер 124(1), С. 13 - 26

Опубликована: Ноя. 26, 2020

Despite being the hallmark of cancer that is responsible for highest number deaths, very little known about biology metastasis. Metastatic disease typically manifests after a protracted period undetectable following surgery or systemic therapy, owing to relapse recurrence. In case breast cancer, metastatic can occur months decades initial diagnosis and treatment. this review, we provide an overview key factors influence recurrence, with goal highlighting critical unanswered questions still need be addressed make difference in mortality patients.

Язык: Английский

Процитировано

456
Targeted protein degradation: mechanisms, strategies and application DOI Creative Commons
Lin Zhao, Jia Zhao,

Kunhong Zhong

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Апрель 4, 2022

Abstract Traditional drug discovery mainly focuses on direct regulation of protein activity. The development and application activity modulators, particularly inhibitors, has been the mainstream in development. In recent years, PROteolysis TArgeting Chimeras (PROTAC) technology emerged as one most promising approaches to remove specific disease-associated proteins by exploiting cells’ own destruction machinery. addition PROTAC, many different targeted degradation (TPD) strategies including, but not limited to, molecular glue, Lysosome-Targeting Chimaera (LYTAC), Antibody-based PROTAC (AbTAC), are emerging. These technologies have only greatly expanded scope TPD, also provided fresh insights into discovery. Here, we summarize advances major TPD technologies, discuss their potential applications, hope provide a prime for both biologists chemists who interested this vibrant field.

Язык: Английский

Процитировано

446
Protein degraders enter the clinic — a new approach to cancer therapy DOI

Deborah Chirnomas,

Keith R. Hornberger, Craig M. Crews

и другие.

Nature Reviews Clinical Oncology, Год журнала: 2023, Номер 20(4), С. 265 - 278

Опубликована: Фев. 13, 2023

Язык: Английский

Процитировано

359
Epigenetic mechanisms in breast cancer therapy and resistance DOI Creative Commons
Liliana Garcia-Martinez, Yusheng Zhang,

Yuichiro Nakata

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Март 19, 2021

The majority of breast cancers express the estrogen receptor (ERα) and agents targeting this pathway represent main treatment modality. Endocrine therapy has proven successful in hormone-responsive cancer since its early adoption 1940s as an ablative therapy. Unfortunately, therapeutic resistance arises, leading to disease recurrence relapse. Recent studies increased our understanding how changes chromatin landscape deregulation epigenetic factors orchestrate resistant phenotype. Here, we will discuss epigenome is integral determinant hormone response why are promising targets for overcoming clinical resistance.

Язык: Английский

Процитировано

341
Ferroptosis surveillance independent of GPX4 and differentially regulated by sex hormones DOI Creative Commons
Deguang Liang, Yan Feng, Fereshteh Zandkarimi

и другие.

Cell, Год журнала: 2023, Номер 186(13), С. 2748 - 2764.e22

Опубликована: Июнь 1, 2023

Язык: Английский

Процитировано

340
Modulating Glycolysis to Improve Cancer Therapy DOI Open Access
Chaithanya Chelakkot, Vipin Shankar Chelakkot, Young Kee Shin

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2606 - 2606

Опубликована: Янв. 30, 2023

Cancer cells undergo metabolic reprogramming and switch to a ‘glycolysis-dominant’ profile promote their survival meet requirements for energy macromolecules. This phenomenon, also known as the ‘Warburg effect,’ provides advantage cancer make tumor environment more pro-cancerous. Additionally, increased glycolytic dependence promotes chemo/radio resistance. A similar is shown by immune in microenvironment, inducing competition between tumor-infiltrating over nutrients. Several recent studies have that targeting enhanced glycolysis promising strategy them susceptible treatment with other conventional modalities, including chemotherapy, radiotherapy, hormonal therapy, immunotherapy, photodynamic therapy. Although several strategies been developed of are different stages pre-clinical clinical evaluation, there still lack effective specifically target cell improve efficacy. Herein, we reviewed our current understanding role how this phenomenon could be potential efficacy

Язык: Английский

Процитировано

175
A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer DOI Open Access

Léa Clusan,

François Ferrière, Gilles Flouriot

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6834 - 6834

Опубликована: Апрель 6, 2023

Breast cancer is the most common and deadliest among women worldwide. Estrogen signaling closely associated with hormone-dependent breast (estrogen progesterone receptor positive), which accounts for two-thirds of tumors. Hormone therapy using antiestrogens gold standard, but resistance to these treatments invariably occurs through various biological mechanisms, such as changes in estrogen activity, mutations ESR1 gene, aberrant activation PI3K pathway or cell cycle dysregulations. All factors have led development new therapies, selective degraders (SERDs), combination therapies cyclin-dependent kinases (CDK) 4/6 inhibitors. Therefore, understanding essential treatment drug cancers. This mini-review summarizes current literature on signalization, mechanisms action clinical implications receptors cancer.

Язык: Английский

Процитировано

171
Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021 DOI Creative Commons
Qing Wu, Wei Qian,

Xiaoli Sun

и другие.

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Окт. 8, 2022

Abstract The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, gene therapy products) have approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 these were identified cancer therapeutics cancer-related drugs, 120 them classified therapeutic for solid tumors according to their initial indications. These evolved from small molecules with broad-spectrum antitumor properties early stage monoclonal antibodies (mAbs) antibody‒drug conjugates (ADCs) more precise targeting effect during most recent decade. extended indications other malignancies, constituting treatment system monotherapy combined therapy. However, available targets are still mainly limited receptor tyrosine kinases (RTKs), restricting development drugs. In this review, summarized indications, characteristics, functions. Additionally, RTK-targeted therapies immune checkpoint-based immunotherapies also discussed. Our analysis existing challenges potential opportunities may advance tumor future.

Язык: Английский

Процитировано

140
Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management DOI Creative Commons
Ping Jin, Jingwen Jiang, Li Zhou

и другие.

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Июль 18, 2022

Drug resistance represents a major obstacle in cancer management, and the mechanisms underlying stress adaptation of cells response to therapy-induced hostile environment are largely unknown. As central organelle for cellular energy supply, mitochondria can rapidly undergo dynamic changes integrate signaling pathways provide bioenergetic biosynthetic flexibility cells, which contributes multiple aspects tumor characteristics, including drug resistance. Therefore, targeting therapy overcoming has attracted increasing attention various types cancer. Multiple mitochondrial processes, dynamics, metabolism, apoptotic regulatory machinery, have been demonstrated be potential targets. However, recent insights into revealed complexity structure functions, elusive functions biology, inaccessibility mitochondria, posed challenges clinical application mitochondrial-based therapeutic strategies. discovery both novel mitochondria-targeting agents innovative approaches is urgently required. Here, we review most literature summarize molecular their intricate connection with In addition, an overview emerging strategies target effectively chemoresistance highlighted, emphasis on repositioning delivery approaches, may accelerate compounds therapy.

Язык: Английский

Процитировано

133