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

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 15058

Special Issue Editors

Prof. Dr. Michael Bohlmann

E-Mail Website
Guest Editor
Department of Obstetrics and Gynecology, St. Elisabeth Hospital Loerrach, 79539 Loerrach, Germany
Interests: breast cancer; gynecological malignancies; targeted therapy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ralf D. Hofheinz

E-Mail Website
Guest Editor
Department of Medical Oncology, University Hospital Mannheim, 68167 Mannheim, Germany
Interests: pancreatic cancer; metastatic colorectal cancer; oesophageal squamous cell cancer; rectal cancer; gastric cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The introduction of an antibody-based treatment was a major milestone in therapy in patients with solid tumors, improving outcomes such as disease-free and progression-free survival as well as overall survival. This is especially true for Her2-neu-positive patients with breast or gastric cancer, both in the (neo-) adjuvant and metastatic setting. The expression of the Her2neu antigen, however, is not limited to those distinct tumor types.In recent years, therapeutic approaches expanded from therapies with antibodies and chemotherapy to the introduction of antibody–drug conjugates (ADC). In advanced stages, tumor heterogeneity caused by both overexpression or downregulation of specific antigens as well as clonal progression may play a crucial role in the development of drug resistance. Analyzing the efficacy of targeted therapies by examining the Her2 status in liquid biopsies based on circulating tumor cells offers modalities for real-time monitoring of disease progression and therapeutic response.This Special Issue aims to deepen the understanding of novel prognostic surrogate markers and target structures and treatment response parameters for Her2-positive cancer entities and their significance for clinical decision making. We welcome submissions that will contribute to the individualization of systemic therapy based on targeting the Her2 /ERBB2 pathways and that could generate additional predictive factors of an antibody-based systemic therapy.

Prof. Dr. Michael Bohlmann
Prof. Ralf D. Hofheinz
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Her2-neu-positive cancers
  • targeted therapy
  • circulating tumor cells
  • drug resistance

Published Papers (6 papers)

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Editorial

Jump to: Research, Review

3 pages, 197 KiB  
Editorial
HER-2-Positive Tumors: A Continuously Evolving Field in Cancer Research
by Ralf Hofheinz, Sylvie Lorenzen and Michael K. Bohlmann
Cancers 2023, 15(13), 3333; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15133333 - 25 Jun 2023
Viewed by 884
Abstract
Almost 25 years ago, trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2), was licensed for the treatment of patients with metastatic HER2-positive breast cancer in the United States of America (USA) [...] Full article
(This article belongs to the Special Issue Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments)

Research

Jump to: Editorial, Review

20 pages, 1617 KiB  
Article
Immune Markers and Tumor-Related Processes Predict Neoadjuvant Therapy Response in the WSG-ADAPT HER2-Positive/Hormone Receptor-Positive Trial in Early Breast Cancer
by Nadia Harbeck, Raquel von Schumann, Ronald Ernest Kates, Michael Braun, Sherko Kuemmel, Claudia Schumacher, Jochem Potenberg, Wolfram Malter, Doris Augustin, Bahriye Aktas, Helmut Forstbauer, Joke Tio, Eva-Maria Grischke, Claudia Biehl, Cornelia Liedtke, Sanne Lysbet De Haas, Regula Deurloo, Rachel Wuerstlein, Hans Heinrich Kreipe and Oleg Gluz
Cancers 2021, 13(19), 4884; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13194884 - 29 Sep 2021
Cited by 12 | Viewed by 2382
Abstract
Prognostic or predictive biomarkers in HER2-positive early breast cancer (EBC) may inform treatment optimization. The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy. [...] Read more.
Prognostic or predictive biomarkers in HER2-positive early breast cancer (EBC) may inform treatment optimization. The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy. In this exploratory analysis, we evaluated potential early predictors of response to neoadjuvant therapy. The effects of PIK3CA mutations and immune (CD8 and PD-L1) and apoptotic markers (BCL2 and MCL1) on pCR rates were assessed, along with intrinsic BC subtypes. Immune response and pCR were lower in PIK3CA-mutated tumors compared with wildtype. Increased BCL2 at baseline in all patients and at Cycle 2 in the T-DM1 arms was associated with lower pCR. In the T-DM1 arms only, the HER2-enriched subtype was associated with increased pCR rate (54% vs. 28%). These findings support further prospective pCR-driven de-escalation studies in patients with HER2-positive EBC. Full article
(This article belongs to the Special Issue Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments)
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15 pages, 1293 KiB  
Article
Long-Term Outcomes of a Randomized Study of Neoadjuvant Induction Dual HER2 Blockade with Trastuzumab and Lapatinib Followed by Weekly Paclitaxel Plus Dual HER2 Blockade for HER2-Positive Primary Breast Cancer (Neo-Lath Study)
by Eriko Tokunaga, Norikazu Masuda, Naohito Yamamoto, Hiroji Iwata, Hiroko Bando, Tomoyuki Aruga, Shoichiro Ohtani, Tomomi Fujisawa, Toshimi Takano, Kenichi Inoue, Nobuyasu Suganuma, Masahiro Takada, Kenjiro Aogi, Kenichi Sakurai, Hideo Shigematsu, Katsumasa Kuroi, Hironori Haga, Shinji Ohno, Satoshi Morita and Masakazu Toi
Cancers 2021, 13(16), 4008; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13164008 - 09 Aug 2021
Cited by 3 | Viewed by 2714
Abstract
We conducted the Neo-LaTH study in which patients were randomized to different lengths of neoadjuvant induction anti-HER2 therapy with lapatinib and trastuzumab followed by weekly paclitaxel plus the anti-HER2 therapy, and in estrogen receptor (ER)-positive patients, with or without concurrent endocrine therapy. The [...] Read more.
We conducted the Neo-LaTH study in which patients were randomized to different lengths of neoadjuvant induction anti-HER2 therapy with lapatinib and trastuzumab followed by weekly paclitaxel plus the anti-HER2 therapy, and in estrogen receptor (ER)-positive patients, with or without concurrent endocrine therapy. The use of endocrine therapy did not affect the response; comprehensive pathological complete response (CpCR) plus ypN0 rate was 57.6% and 30.3% in ER-negative and ER-positive patients, respectively. After surgery, patients received an anthracycline-based regimen based on physician’s choice, followed by trastuzumab for 1 year, and in ER-positive patients, endocrine therapy for 5 years. Here, we report the 5-year survival outcomes. Among the followed-up patients (n = 212), the 5-year disease-free survival (DFS), distant DFS, and overall survival rates were 87.8% [95% confidence interval (CI), 82.5–91.6%], 93.7% (95% CI, 89.3–96.3%), and 95.6% (95% CI, 91.7–97.7%), respectively, with no difference between ER-negative and ER-positive patients. The 5-year DFS rate was significantly higher in patients who had a CpCR plus ypN0 after neoadjuvant treatment than in those who did not (91.7% vs. 85.1%; p = 0.0387). The stratified analysis showed better survival outcomes in patients who had CpCRypN0 than in those who did not after neoadjuvant treatment, regardless of use of adjuvant anthracycline therapy. Full article
(This article belongs to the Special Issue Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments)
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22 pages, 37633 KiB  
Article
Imaging-Guided Therapy Simultaneously Targeting HER2 and EpCAM with Trastuzumab and EpCAM-Directed Toxin Provides Additive Effect in Ovarian Cancer Model
by Tianqi Xu, Anzhelika Vorobyeva, Alexey Schulga, Elena Konovalova, Olga Vorontsova, Haozhong Ding, Torbjörn Gräslund, Liubov A. Tashireva, Anna Orlova, Vladimir Tolmachev and Sergey M. Deyev
Cancers 2021, 13(16), 3939; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13163939 - 04 Aug 2021
Cited by 8 | Viewed by 3213
Abstract
Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression of human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM) in approx. 30% and 70% of ovarian cancers, respectively, allows for co-targeted treatment. [...] Read more.
Efficient treatment of disseminated ovarian cancer (OC) is challenging due to its heterogeneity and chemoresistance. Overexpression of human epidermal growth factor receptor 2 (HER2) and epithelial cell adhesion molecule (EpCAM) in approx. 30% and 70% of ovarian cancers, respectively, allows for co-targeted treatment. The clinical efficacy of the monoclonal antibody trastuzumab in patients with HER2-positive breast, gastric and gastroesophageal cancers makes it readily available as the HER2-targeting component. As the EpCAM-targeting component, we investigated the designed ankyrin repeat protein (DARPin) Ec1 fused to a truncated variant of Pseudomonas exotoxin A with reduced immunogenicity and low general toxicity (LoPE). Ec1-LoPE was radiolabeled, evaluated in ovarian cancer cells in vitro and its biodistribution and tumor-targeting properties were studied in vivo. The therapeutic efficacy of Ec1-LoPE alone and in combination with trastuzumab was studied in mice bearing EpCAM- and HER2-expressing SKOV3 xenografts. SPECT/CT imaging enabled visualization of EpCAM and HER2 expression in the tumors. Co-treatment using Ec1-LoPE and trastuzumab was more effective at reducing tumor growth and prolonged the median survival of mice compared with mice in the control and monotherapy groups. Repeated administration of Ec1-LoPE was well tolerated without signs of hepatic or kidney toxicity. Co-treatment with trastuzumab and Ec1-LoPE might be a potential therapeutic strategy for HER2- and EpCAM-positive OC. Full article
(This article belongs to the Special Issue Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments)
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Review

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16 pages, 450 KiB  
Review
Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence
by Kamel Debbi, Noémie Grellier, Gokoulakrichenane Loganadane, Chahrazed Boukhobza, Mathilde Mahé, Mohamed Aziz Cherif, Hanan Rida, Joseph Gligorov and Yazid Belkacemi
Cancers 2023, 15(8), 2278; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15082278 - 13 Apr 2023
Cited by 6 | Viewed by 3078
Abstract
Purpose: Over the past twenty years, anti-HER2 targeted therapies have proven to be a revolution in the management of human epidermal growth receptor 2 (HER2)-positive breast cancers. Anti-HER2 therapies administered alone or in combination with chemotherapy have been specifically studied. Unfortunately, the [...] Read more.
Purpose: Over the past twenty years, anti-HER2 targeted therapies have proven to be a revolution in the management of human epidermal growth receptor 2 (HER2)-positive breast cancers. Anti-HER2 therapies administered alone or in combination with chemotherapy have been specifically studied. Unfortunately, the safety of anti-HER2 therapies in combination with radiation remains largely unknown. Thus, we propose a literature review of the risks and safety of combining radiotherapy with anti-HER2 therapies. We will focus on the benefit/risk rationale and try to understand the risk of toxicity in early-stage and advanced breast cancer. Methods: Research was carried out on the following databases: PubMed, EMBASE, ClinicalTrial.gov, Medline, and Web of Science for the terms “radiotherapy”, “radiation therapy”, “radiosurgery”, “local ablative therapy”, and “stereotactic”, combined with “trastuzumab”, “pertuzumab”, “trastuzumab emtansine”, “TDM-1”, “T-Dxd”, “trastuzumab deruxtecan”, “tucatinib”, “lapatinib”, “immune checkpoint inhibitors”, “atezolizumab”, “pembrolizumab”, “nivolumab”, “E75 vaccine”, “interferon”, “anti-IL-2”, “anti-IL 12”, and “ADC”. Results: Association of radiation and monoclonal antibodies such as trastuzumab and pertuzumab (with limited data) seems to be safe, with no excess risk of toxicity. Preliminary data with radiation and of antibody–drug conjugate of trastuzumab combined cytotoxic (trastuzumab emtansine, trastuzumab deruxtecan), given the underlying mechanism of action, suggest that one must be particularly cautious with the association. The safety of the combination of a tyrosine kinase inhibitor (lapatinib, tucatinib) and radiation remains under-studied. The available evidence suggests that checkpoint inhibitors can be safely administrated with radiation. Conclusions: HER2-targeting monoclonal antibodies and checkpoint inhibitors can be combined with radiation, apparently with no excess toxicities. Caution is required when associating radiation with TKI and antibody drugs, considering the limited evidence. Full article
(This article belongs to the Special Issue Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments)
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22 pages, 2203 KiB  
Review
Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments
by Serafin Morales, Ariadna Gasol and Douglas Rene Sanchez
Cancers 2021, 13(22), 5771; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13225771 - 18 Nov 2021
Cited by 7 | Viewed by 1997
Abstract
HER2 positive breast cancer represent about 20% of all breast cancer subtypes and it was considered the subtype with the worst prognosis until the discovery of therapies directed against the HER2 protein. The determination of the status of the HER2 must be very [...] Read more.
HER2 positive breast cancer represent about 20% of all breast cancer subtypes and it was considered the subtype with the worst prognosis until the discovery of therapies directed against the HER2 protein. The determination of the status of the HER2 must be very precise and well managed to identify this subtype, and there are very specific and updated guides that allow its characterization to be adjusted. Treatment in local disease has been considerably improved with less aggressive and highly effective approaches and very high cure rates. In metastatic disease, average median survival rates of 5 years have been achieved. New highly active molecules have also been discovered that allow disease control in very complicated situations. This article reviews all these options that can be used for the management of this disease. Full article
(This article belongs to the Special Issue Her2-Positive Cancers and Antibody-Based Treatment: State of the Art and Future Developments)
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