Deciphering breast cancer: from biology to the clinic

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1708 - 1728

Published: March 16, 2023

Language: Английский

---

The CDK4/6 inhibitor revolution — a game-changing era for breast cancer treatment

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 21(2), P. 89 - 105

Published: Dec. 11, 2023

Language: Английский

---

Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023

Annals of Oncology, Journal Year: 2023, Volume and Issue: 34(11), P. 970 - 986

Published: Sept. 6, 2023

The 18th St Gallen International Breast Cancer Conference held in March 2023, Vienna, Austria, assessed significant new findings for local and systemic therapies early breast cancer with a focus on the evaluation of multimodal treatment options. emergence more effective, innovative agents both preoperative (primary or neoadjuvant) post-operative (adjuvant) settings has underscored pivotal role multidisciplinary approach decision making, particularly when selecting therapy an individual patient. importance discussions regarding clinical benefits interventions was explicitly emphasized by consensus panel as integral part developing optimal plan 'right' degree intensity duration. panelists focused controversies surrounding management common ductal/no special type lobular histology, which account vast majority tumors. expert opinion based interpretations available data, well current practices their professional environments, personal socioeconomic factors affecting patients, cognizant varying reimbursement accessibility constraints around world. strongly advocated patient participation well-designed studies whenever feasible. With these considerations mind, Consensus aims to offer guidance clinicians appropriate treatments early-stage assist balancing realistic trade-offs between benefit toxicity, enabling patients make well-informed choices through shared decision-making process.

Language: Английский

---

An emerging generation of endocrine therapies in breast cancer: a clinical perspective

npj Breast Cancer, Journal Year: 2023, Volume and Issue: 9(1)

Published: April 5, 2023

Abstract Anti-estrogen therapy is a key component of the treatment both early and advanced-stage hormone receptor (HR)-positive breast cancer. This review discusses recent emergence several anti-estrogen therapies, some which were designed to overcome common mechanisms endocrine resistance. The new generation drugs includes selective estrogen modulators (SERMs), orally administered degraders (SERDs), as well more unique agents such complete antagonists (CERANs), proteolysis targeting chimeric (PROTACs), covalent (SERCAs). These are at various stages development being evaluated in metastatic settings. We discuss efficacy, toxicity profile, completed ongoing clinical trials for each drug highlight differences their activity study population that have ultimately influenced advancement.

Language: Английский

---

Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(1), P. e2351700 - e2351700

Published: Jan. 22, 2024

Importance Tissue-based next-generation sequencing (NGS) of solid tumors is the criterion standard for identifying somatic mutations that can be treated with National Comprehensive Cancer Network guideline–recommended targeted therapies. Sequencing circulating tumor DNA (ctDNA) also identify tumor-derived mutations, and there increasing clinical evidence supporting ctDNA testing as a diagnostic tool. The value concurrent tissue profiling has not been formally assessed in large, multicancer cohort from heterogeneous settings. Objective To evaluate whether patients concurrently tested both NGS have higher rate detection guideline-based compared alone. Design, Setting, Participants This study comprised 3209 who underwent between May 2020, December 2022, within deidentified, Tempus multimodal database, consisting linked molecular data. Included had stage IV disease (non–small cell lung cancer, breast prostate or colorectal cancer) sufficient blood sample quantities analysis. Exposures Received results plasma genomic profiling, biopsies draws occurring 30 days one another. Main Outcomes Measures Detection rates variants found uniquely by profiling. Results (median age at diagnosis disease, 65.3 years [2.5%-97.5% range, 43.3-83.3 years]) included 1693 women (52.8%). Overall, 1448 (45.1%) variant detected. Of these patients, 9.3% (135 1448) detected 24.2% (351 solid-tissue testing. Although largely concordant another, differences identification actionable either assay varied according to cancer type, gene, variant, burden. 352 20.2% (71 352) unique findings results. Most unique, (55.0% [55 100]) were ESR1 , resulting 24.7% increase (23 93) harboring an mutation relative Conclusions Relevance suggests biomarkers are testing, among cancer. Integration into routine management advanced cancers may expand delivery molecularly guided therapy improve patient outcomes.

Language: Английский

---

Interpreting and integrating genomic tests results in clinical cancer care: Overview and practical guidance

CA A Cancer Journal for Clinicians, Journal Year: 2024, Volume and Issue: 74(3), P. 264 - 285

Published: Jan. 4, 2024

Abstract The last decade has seen rapid progress in the use of genomic tests, including gene panels, whole‐exome sequencing, and whole‐genome research clinical cancer care. These advances have created expansive opportunities to characterize molecular attributes cancer, revealing a subset cancer‐associated aberrations called driver mutations . identification these can unearth vulnerabilities cells targeted therapeutics, which led development approval novel diagnostics personalized interventions various malignancies. applications this modern approach, often referred as precision oncology or medicine , are already becoming staple care will expand exponentially over coming years. Although tests lead better outcomes by informing risk, prognosis, therapeutic selection, they remain underutilized routine A contributing factor is lack understanding their utility difficulty results interpretation broad community. Practical guidelines on how interpret integrate information setting, addressed clinicians without expertise genomics, currently limited. Building upon foundations concept oncology, authors developed practical guidance aid test that help inform decision making for patients with cancer. They also discuss challenges prevent wider implementation oncology.

Language: Английский

---

Therapies for the Treatment of Advanced/Metastatic Estrogen Receptor-Positive Breast Cancer: Current Situation and Future Directions

Cancers, Journal Year: 2024, Volume and Issue: 16(3), P. 552 - 552

Published: Jan. 27, 2024

The hormone receptor-positive (HR+) type is the most frequently identified subtype of breast cancer. HR+ cancer has a more positive prognosis when compared to other subtypes, such as human epidermal growth factor protein 2-positive disorder and triple-negative disease. advancement in treatment outcomes for advanced been considerably elevated due discovery cyclin-dependent kinase 4/6 inhibitors their combination effects with endocrine therapy. However, despite considerable effectiveness tamoxifen, selective estrogen receptor modulator (SERMs), aromatase (AI), issue resistance still presents significant challenge As result, there focus on exploring new therapeutic strategies targeted degradation covalent inhibition targeting ERα. This article discusses latest progress treatments like oral ER degraders (SERDs), complete antagonists (CERANs), (SERCAs), proteolysis chimera (PROTAC) degraders, combinations CDK4/6 specifically those compounds that have transitioned into phases clinical development.

Language: Английский

---

Use of ctDNA in early breast cancer: analytical validity and clinical potential

npj Breast Cancer, Journal Year: 2024, Volume and Issue: 10(1)

Published: June 19, 2024

Abstract Circulating free tumor DNA (ctDNA) analysis is gaining popularity in precision oncology, particularly metastatic breast cancer, as it provides non-invasive, real-time information to complement tissue biopsies, allowing for tailored treatment strategies and improved patient selection clinical trials. Its use early cancer has been limited so far, due the relatively low sensitivity of available techniques a setting characterized by lower levels ctDNA shedding. However, advances sequencing bioinformatics, well methylome profiles, have led an increasing interest application from screening curative evaluation minimal residual disease (MRD) detection. With multiple prospective trials this setting, may become useful practice. This article reviews data regarding analytical validity currently tests detection potential cancer.

Language: Английский

---

Circulating tumor DNA validity and potential uses in metastatic breast cancer

npj Breast Cancer, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 12, 2024

Abstract Following the first characterization of circulating tumor DNA (ctDNA) in 1990s, recent advances led to its introduction clinics. At present, European Society Of Medical Oncology (ESMO) recommendations endorse ctDNA testing routine clinical practice for genotyping direct molecularly targeted therapies patients with metastatic cancer. In studies on breast cancer, has been utilized treatment tailoring, tracking mechanisms drug resistance, and predicting disease response before imaging. We review available evidence regarding applications

Language: Английский

---

Cyclin-dependent protein kinases and cell cycle regulation in biology and disease

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 12, 2025

Abstract Cyclin Dependent Kinases (CDKs) are closely connected to the regulation of cell cycle progression, having been first identified as kinases able drive division. In reality, human genome contains 20 different CDKs, which can be divided in at least three sub-family with functions, mechanisms regulation, expression patterns and subcellular localization. Most these play fundamental roles normal physiology eucaryotic cells; therefore, their deregulation is associated onset and/or progression multiple disease including but not limited neoplastic neurodegenerative conditions. Here, we describe functions categorized into main functional groups they classified, highlighting most relevant pathways that functions. We then discuss potential CDKs pathologies, a particular focus on cancer, have extensively studied explored therapeutic targets. Finally, how inhibitors become standard therapies selected cancers propose novel ways investigation export targeting from cancer other chronic diseases. hope effort made collecting all available information both prominent lesser-known CDK family members will help identify develop areas research improve lives patients affected by debilitating

Language: Английский

---