HER2-targeted therapies in cancer: a systematic review

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Фев. 2, 2024

Abstract Abnormal alterations in human epidermal growth factor receptor 2 (HER2, neu, and erbB2) are associated with the development of many tumors. It is currently a crucial treatment for multiple cancers. Advanced molecular biology further exploration HER2-mediated pathway have promoted medicine design combination drug regimens. An increasing number HER2-targeted drugs including specific monoclonal antibodies, tyrosine kinase inhibitors (TKIs), antibody-drug conjugates (ADCs) been approved by U.S. Food Drug Administration. The emergence ADCs, has significantly transformed landscape various tumors, such as breast, gastric, bladder cancer. Classic antibodies novel TKIs not only demonstrated remarkable efficacy, but also expanded their indications, ADCs particular exhibiting profound clinical applications. Moreover concept low HER2 expression signifies breakthrough therapy, indicating that an tumors patients will benefit from this approach. This article, provides comprehensive review underlying mechanism action, representative drugs, corresponding trials, recent advancements, future research directions pertaining to therapy.

Язык: Английский

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Exploring Biomarkers in Breast Cancer: Hallmarks of Diagnosis, Treatment, and Follow-Up in Clinical Practice

Medicina, Год журнала: 2024, Номер 60(1), С. 168 - 168

Опубликована: Янв. 17, 2024

Breast cancer is a prevalent malignancy in the present day, particularly affecting women as one of most common forms cancer. A significant portion patients initially with localized disease, for which curative treatments are pursued. Conversely, another substantial segment diagnosed metastatic has worse prognosis. Recent years have witnessed profound transformation prognosis this latter group, primarily due to discovery various biomarkers and emergence targeted therapies. These biomarkers, encompassing serological, histological, genetic indicators, demonstrated their value across multiple aspects breast management. They play crucial roles initial diagnosis, aiding detection relapses during follow-up, guiding application treatments, offering valuable insights prognostic stratification, especially highly aggressive tumor types. Molecular markers now become keystone given diverse array chemotherapy options treatment modalities available. signify transformative shift arsenal therapeutic against Their diagnostic precision enables categorization tumors elevated risks recurrence, increased aggressiveness, heightened mortality. Furthermore, existence therapies tailored target specific molecular anomalies triggers cascade changes behavior. Therefore, primary objective article offer comprehensive review clinical, diagnostic, prognostic, utility principal currently use, well clinical impact on In doing so, our goal contribute more comprehension complex disease and, ultimately, enhance patient outcomes through precise effective strategies.

Язык: Английский

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Molecular Targeting of the Human Epidermal Growth Factor Receptor-2 (HER2) Genes across Various Cancers

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 1064 - 1064

Опубликована: Янв. 15, 2024

Human epidermal growth factor receptor 2 (HER2) belongs to the ErbB family, a group of four transmembrane glycoproteins with tyrosine kinase activity, all structurally related (EGFR). These kinases are involved in transmission cellular signals controlling normal cell and differentiation. If this goes awry, it can lead dysregulated cell. HER2 specifically be implicated pathogenesis at least eight malignancies. positivity quickly became well-characterized indicator aggressiveness poor prognosis, high rates disease progression mortality. After realizing implication HER2, first investigated as target for treatment breast cancer, later expanded areas research other cancer types. To day, most therapeutic advancements anti-HER2 therapy have been cancer; however, there strong made incorporation types well. This comprehensive review dissects its core, incorporating up date information. The topics touched upon discussed detail 200 published sources from highly recognized journals integrated. importance knowing about is exemplified by groundbreaking that made, change plans has brought oncological world last twenty years. Since discovery significant breakthroughs knowledge regarding actual receptor, receptors biology, mechanism action, tests detect strides on how best incorporate targeted treatment. Due success field thus far, concludes discussing future novel currently development everyone should aware of.

Язык: Английский

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Current Biological, Pathological and Clinical Landscape of HER2-Low Breast Cancer

Cancers, Год журнала: 2022, Номер 15(1), С. 126 - 126

Опубликована: Дек. 25, 2022

HER2-low breast cancer (BC) is a newly defined subset of HER2-negative BC that has HER2 immunohistochemical (IHC) score 1+ or 2+/in situ hybridization (ISH) negative phenotype. Recent clinical trials have demonstrated significant benefits novel directing antibody-drug conjugates (ADCs) in treating this group tumors. Trastuzumab-deruxtecan (T-Dxd), HER2-directing ADC was recently approved by the U.S. Food and Drug Administration as first targeted therapy to treat BC. However, still not well characterized clinically pathologically. This review aims update current biological, pathological landscape based on English literature published past two years propose future directions management, pathology practice, translational research We hope it would help better understand tumor biology efforts for identifying recognized targetable

Язык: Английский

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Clinical perspective: Antibody-drug conjugates for the treatment of HER2-positive breast cancer

Molecular Therapy, Год журнала: 2023, Номер 31(7), С. 1874 - 1903

Опубликована: Март 22, 2023

Antibody-drug conjugates (ADCs) are a promising class of cancer biopharmaceuticals that exploit the specificity monoclonal antibody (mAb) to selectively deliver highly cytotoxic small molecules targeted cells, leading an enhanced therapeutic index through increased antitumor activity and decreased off-target toxicity. ADCs hold great promise for treatment patients with human epidermal growth factor receptor 2 (HER2)-positive breast after approval tremendous success trastuzumab emtansine deruxtecan, representing turning point in both HER2-positive ADC technology. Additionally importantly, total 29 candidates now being investigated different stages clinical development cancer. The purpose this review is provide insight into field present comprehensive overview approved or under investigation

Язык: Английский

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Interobserver and Interantibody Reproducibility of HER2 Immunohistochemical Scoring in an Enriched HER2-Low–Expressing Breast Cancer Cohort

American Journal of Clinical Pathology, Год журнала: 2023, Номер 159(5), С. 484 - 491

Опубликована: Фев. 28, 2023

We assessed the interobserver and interantibody reproducibility of HER2 immunohistochemical scoring in an enriched HER2-low-expressing breast cancer cohort.A total 114 specimens were stained by HercepTest (Agilent Dako) PATHWAY anti-HER2 (4B5) (Ventana) antibody assays scored 6 pathologists independently using current guidelines. Level agreement was evaluated Cohen κ analysis.Although rate for both antibodies achieved substantial agreement, average significantly higher than that 4B5 clone (74.3% vs 65.1%; P = .002). The overall between 2 57.8%. Complete concordance 44.7% cases 45.6% 4B5. Absolute rates increased from 0-1+ (78.1% 72.2% 4B5; moderate agreement) to 2-3+ (91.9% 86.3% almost perfect agreement).Our results demonstrated notable variation on evaluating immunohistochemistry, especially with scores 0-1+, although performance much more improved among breast-specialized awareness HER2-low concept. More accurate reproducible methods are needed selecting patients who may benefit newly approved HER2-targeting agent cancers.

Язык: Английский

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Pathological identification of HER2-low breast cancer: Tips, tricks, and troubleshooting for the optimal test

Frontiers in Molecular Biosciences, Год журнала: 2023, Номер 10

Опубликована: Апрель 3, 2023

The introduction of novel anti-HER2 antibody-drug conjugates (ADC) for the treatment HER2-low breast cancers has transformed traditional dichotomy HER2 status to an expanded spectrum. However, identification (i.e., immunohistochemistry (IHC) score 1 + or IHC 2+, without gene amplification) tumors is challenged by methodological and analytical variables that might influence sensitivity reproducibility testing. To open all possible therapeutic opportunities cancer patients implementation more accurate reproducible testing strategies mandatory. Here, we provide overview existing barriers may trouble in discuss practical solutions could enhance HER-low assessment.

Язык: Английский

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HER2 evaluation for clinical decision making in human solid tumours: pearls and pitfalls

Histopathology, Год журнала: 2024, Номер 85(1), С. 3 - 19

Опубликована: Март 5, 2024

The significant clinical benefits of human epidermal growth factor receptor 2 (HER2)‐targeted therapeutic agents have revolutionized the treatment landscape in a variety solid tumours. Accordingly, accurate evaluation HER2 status these different tumour types is critical for decision making to select appropriate patients who may benefit from life‐saving HER2‐targeted therapies. biomarker scoring criteria organ systems, and close adherence corresponding testing guidelines their updates, if available, essential evaluation. In addition, knowing unusual patterns expression also important avoid inaccurate this review, we discuss key considerations when evaluating tumours making, including tissue handling preparation testing, as well pathologist's readout results breast carcinomas, gastroesophageal adenocarcinomas, colorectal gynaecologic non‐small cell lung carcinomas.

Язык: Английский

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Standard-of-Care Treatment for HER2+ Metastatic Breast Cancer and Emerging Therapeutic Options

Breast Cancer Basic and Clinical Research, Год журнала: 2024, Номер 18

Опубликована: Янв. 1, 2024

Prior to the advent of HER2-targeted monoclonal antibody trastuzumab, HER2+ breast cancer (BC) was considered an aggressive disease with a poor prognosis. Over past 25 years, innovations in molecular biology, pathology, and early therapeutics have transformed treatment landscape. With multiple HER2-directed therapies, there been immense improvements oncological outcomes both adjuvant metastatic settings. Currently, 8 therapies are approved by Food Drug Administration (FDA) for early-stage and/or advanced/metastatic disease. Nonetheless, approximately 25% patients develop recurrent or metastasis after therapy most (MBC) die from their Given many mechanisms resistance therapy, is pressing need further personalize care MBC, identification reliable predictive biomarkers, development novel combination regimens overcome therapeutic resistance. Of particular interest established antibody-drug conjugates, as well other multifaceted approaches harness immune system (checkpoint inhibitors, bispecific antibodies, vaccine therapy). Herein, we discuss standard-of-care including management brain metastases (BCBM). Furthermore, highlight endeavors ongoing controversies challenges.

Язык: Английский

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Analytical and clinical validation of PATHWAY Anti-HER-2/neu (4B5) antibody to assess HER2-low status for trastuzumab deruxtecan treatment in breast cancer

Virchows Archiv, Год журнала: 2023, Номер 484(6), С. 1005 - 1014

Опубликована: Окт. 20, 2023

In DESTINY-Breast04 (DB-04), safety and efficacy of HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in previously treated HER2-low unresectable/metastatic breast cancer were established. This manuscript describes the analytical validation PATHWAY Anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (PATHWAY HER2 (4B5)) to assess status its clinical performance DB-04. Preanalytical processing tissue staining parameters evaluated determine their impact on scoring. The recommended antibody procedure provided optimal tumor staining, deviations cell conditioning and/or incubation times resulted unacceptable negative control changes. Comparisons between lots, kit instruments, day-to-day runs showed overall percent agreements (OPAs) exceeding 97.9%. Inter-laboratory reproducibility OPAs ≥97.4% for all study endpoints. was utilized DB-04 patient selection using 1340 samples (59.0% metastatic, 40.7% primary, (0.3% missing data); 74.3% biopsy, 25.7% resection/excisions). Overall, 77.6% (823/1060) by both central local testing, with level concordance differing sample region origin collection date. DB-04, T-DXd over chemotherapy physician's choice consistent, regardless characteristics used (primary or archival, newly collected, biopsy excision/resection). These results demonstrate that is precise reproducible scoring can be multiple types reliably identifying patients whose tumors have expression are likely derive benefit from T-DXd.

Язык: Английский

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