Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments

Morales, Serafín; Gasol, Ariadna; Sanchez, Douglas

doi:10.3390/cancers13225771

Cited by 8 publications

(6 citation statements)

References 73 publications

(79 reference statements)

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“…Disappointingly, clinical trials have also not yet demonstrated a synergistic effect of immunotherapy and HER2-targeting agents. Studies examining the potential of immune checkpoint inhibitors in metastatic HER2-positive BC patients have yielded low anti-tumour efficacy in unselected, heavily pretreated patients, with limited activity mostly being seen in PD-L1-positive tumours 29 – 31 . The early stages of cancer, which is usually confined to the breast, involve a less invasive tumour and a more permissive microenvironment allowing the immune system to recognise and respond to tumour antigens.…”

Section: Methodsmentioning

confidence: 99%

Adoption and use of immunotherapy in breast cancer management in Africa: barriers and prospect – a narrative review

Mutiu Alani,

Olaoye,

Adesina Abass

2023

Annals of Medicine &Amp; Surgery

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Breast cancer (BC) is the world’s most frequently diagnosed cancer in women, with 7.8 million women diagnosed with breast cancer in the past five years. BC has the highest incidence rate of all cancers in women worldwide (1.67 million), accounting for over 500,000 deaths annually. In Africa, breast cancer accounts for 28% of all cancer and 20% of all cancer deaths in women. The African continent has recorded an alarming increase in incidence, with the highest mortality rate globally. Despite BC being a major health concern in Africa, there is limited access to adequate healthcare services to combat the growing need. Immunotherapy, a promising treatment approach that harnesses the immune system’s power to fight cancer, has shown great potential in breast cancer management. However, in the face of the growing body of evidence supporting its effectiveness, the adoption and use of immunotherapy in breast cancer management in Africa remain limited. Hence, this review aimed to explore the barriers and prospects of immunotherapy adoption and use in breast cancer management in Africa. A comprehensive search across various databases and sources using specific keywords related to immunotherapy and breast cancer to achieve the study aim was conducted. The criteria for including data in the study were based on relevance and availability in English, with no publication year restrictions. The collected data underwent narrative analysis, supplemented by information from sources like country reports, newsletters, commentaries, policy briefs, and direct Google searches. By identifying the challenges and opportunities, this review provided insights into how healthcare providers, policymakers, and other stakeholders can work together to improve the availability and accessibility of immunotherapy to breast cancer patients in Africa.

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Section: Methodsmentioning

confidence: 99%

Adoption and use of immunotherapy in breast cancer management in Africa: barriers and prospect – a narrative review

Mutiu Alani,

Olaoye,

Adesina Abass

2023

Annals of Medicine &Amp; Surgery

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“…1 In the hormone receptor-positive (HR1)/HER21 subpopulation in the KRISTINE trial, neoadjuvant T-DM1 1 pertuzumab and docetaxel 1 carboplatin 1 trastuzumab 1 pertuzumab led to comparable pCR rates (35.1% v 43.8%) and similar invasive disease-free survival (iDFS; hazard ratio [HR], 1.44 [95% CI, 0.54 to 3.88]). 2,3 No predictive markers for T-DM1 have been established so far; particularly, the impact of PIK3CA mutation remains unclear. 4,5 Moreover, several studies indicate that high HER2 expression (by mRNA and/or immunohistochemistry) associates with enhanced benefit from T-DM1.…”

Section: Introductionmentioning

confidence: 99%

De-Escalated Neoadjuvant Trastuzumab-Emtansine With or Without Endocrine Therapy Versus Trastuzumab With Endocrine Therapy in HR+/HER2+ Early Breast Cancer: 5-Year Survival in the WSG-ADAPT-TP Trial

Harbeck

Nitz

Christgen

et al. 2023

JCO

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PURPOSE Neoadjuvant chemotherapy is standard of care in human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC), irrespective of the hormone receptor status. Trastuzumab-emtansine (T-DM1), antibody-drug conjugate, is highly effective in HER2+ EBC; however, no survival data are available for de-escalated antibody-drug conjugate–based neoadjuvant therapy without conventional chemotherapy. PATIENTS AND METHODS In the WSG-ADAPT-TP (ClinicalTrials.gov identifier: NCT01779206 ) phase II trial, 375 centrally reviewed patients with hormone receptor-positive (HR+)/HER2+ EBC (clinical stage I-III) were randomly assigned to 12 weeks of T-DM1 with or without endocrine therapy (ET) or trastuzumab + ET once every 3 weeks (ratio 1:1:1). Adjuvant chemotherapy (ACT) omission was allowed in patients with pathologic complete response (pCR). In this study, we report the secondary survival end points and biomarker analysis. Patients who received at least one dose of study treatment were analyzed. Survival was analyzed using the Kaplan-Meier method, two-sided log-rank statistics, and Cox regression models stratified for nodal and menopausal status. P values < .05 were considered statistically significant. RESULTS T-DM1, T-DM1 + ET, and trastuzumab + ET induced similar 5-year invasive disease-free survival (iDFS; 88.9%, 85.3%, 84.6%; Plog-rank = .608) and overall survival rates (97.2%, 96.4%, 96.3%; Plog-rank = .534). Patients with pCR versus non-pCR had improved 5-year iDFS rates (92.7% v 82.7%; hazard ratio, 0.40; 95% CI, 0.18 to 0.85). Among the 117 patients with pCR, 41 did not receive ACT; 5-year iDFS rates were similar in those with (93.0%; 95% CI, 84.0 to 97.0) and without ACT (92.1%; 95% CI, 77.5 to 97.4; Plog-rank = .848). Translational research revealed that tumors with PIK3CA wild type, high immune marker expression, and luminal-A tumors (by PAM50) had an excellent prognosis with de-escalated anti-HER2 therapy. CONCLUSION The WSG-ADAPT-TP trial demonstrated that pCR after 12 weeks of chemotherapy-free de-escalated neoadjuvant therapy was associated with excellent survival in HR+/HER2+ EBC without further ACT. Despite higher pCR rates for T-DM1 ± ET versus trastuzumab + ET, all trial arms had similar outcomes because of mandatory standard chemotherapy after non-pCR. WSG-ADAPT-TP demonstrated that such de-escalation trials in HER2+ EBC are feasible and safe for patients. Patient selection on the basis of biomarkers or molecular subtypes may increase the efficacy of systemic chemotherapy-free HER2-targeted approaches.

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“…Drug resistance is currently a major problem in several cancers such as UM (uveal melanoma), RCC (renal cell carcinoma), and HNSCC (head and neck squamous cell carcinoma). Although the 1980s was the decade of general radio-chemotherapy with the use of very toxic antitumor drugs and radiation procedures that resulted in numerous side effects, the 2000s was the decade of targeted therapies due to the development of treatments that specifically target driving mutations [ 23 , 24 , 25 ]. Despite the improvements, many of the patients were not cured and suffered relapses.…”

Section: Introductionmentioning

confidence: 99%

New Phenylspirodrimanes from the Sponge-Associated Fungus Stachybotrys chartarum MUT 3308

et al. 2023

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Two phenylspirodrimanes, never isolated before, stachybotrin J (1) and new stachybocin G (epi-stachybocin A) (2), along with the already reported stachybotrin I (3), stachybotrin H (4), stachybotrylactam (5), stachybotrylactam acetate (6), 2α-acetoxystachybotrylactam acetate (7), stachybotramide (8), chartarlactam B (9), and F1839-J (10) were isolated from the sponge-associated fungus Stachybotrys chartarum MUT 3308. Their structures were established based on extensive spectrometric (HRMS) and spectroscopic (1D and 2D NMR) analyses. Absolute configurations of the stereogenic centers of stachybotrin J (1), stachybocin G (2), and stachybotrin I (3), were determined by comparison of their experimental circular dichroism (CD) spectra with their time-dependent density functional theory (TD-DFT) circular dichroism (ECD) spectra. The putative structures of seventeen additional phenylspirodrimanes were proposed by analysis of their respective MS/MS spectra through a Feature-Based Molecular Networking approach. All the isolated compounds were evaluated for their cytotoxicity against five aggressive cancer cell lines (MP41, 786, 786R, CAL33, and CAL33RR), notably including two resistant human cancer cell lines (786R, CAL33RR), and compounds 5, 6, and 7 exhibited cytotoxicity with IC50 values in the range of 0.3−2.2 µM.

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Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments

Cited by 8 publications

References 73 publications

Adoption and use of immunotherapy in breast cancer management in Africa: barriers and prospect – a narrative review

Adoption and use of immunotherapy in breast cancer management in Africa: barriers and prospect – a narrative review

De-Escalated Neoadjuvant Trastuzumab-Emtansine With or Without Endocrine Therapy Versus Trastuzumab With Endocrine Therapy in HR+/HER2+ Early Breast Cancer: 5-Year Survival in the WSG-ADAPT-TP Trial

New Phenylspirodrimanes from the Sponge-Associated Fungus Stachybotrys chartarum MUT 3308

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