Article
Multidisciplinary Sciences
Edward Seung, Zhen Xing, Lan Wu, Ercole Rao, Virna Cortez-Retamozo, Beatriz Ospina, Liqing Chen, Christian Beil, Zhili Song, Bailin Zhang, Mikhail Levit, Gejing Deng, Andrew Hebert, Patrick Kirby, Aiqun Li, Emma-Jane Poulton, Rita Vicente, Audrey Garrigou, Peter Piepenhagen, Greg Ulinski, Michele Sanicola-Nadel, Dinesh S. Bangari, Huawei Qiu, Lily Pao, Dmitri Wiederschain, Ronnie Wei, Zhi-yong Yang, Gary J. Nabel
Summary: A trispecific antibody targeting HER2 and T cells can inhibit breast cancer cell proliferation by stimulating CD4 T cells, and induce tumor regression in a humanized mouse model.
Editorial Material
Oncology
Alicia F. C. Okines, Nicholas C. Turner
Summary: HER2 amplification heterogeneity is linked to resistance to trastuzumab emtansine in the neoadjuvant setting, highlighting the significance of determining whether varying HER2-positive cancer types require distinct treatment approaches.
Review
Oncology
Daniel Eiger, Elisa Agostinetto, Rita Saude-Conde, Evandro de Azambuja
Summary: The article discusses the expression of HER2 in breast cancer and the development of drugs targeting HER2. Patients with HER2-positive breast cancer have higher chances of cure and survival, and now there are also treatments available for patients with lower levels of HER2 expression.
Review
Oncology
G. Nader-Marta, D. Martins-Branco, E. de Azambuja
Summary: HER2-positive breast cancer is a subtype of breast malignancy with aggressive behavior and high recurrence rates. The combination of trastuzumab, pertuzumab, and a taxane remains the preferred first-line therapy. Recent studies have shown that trastuzumab deruxtecan is more effective than trastuzumab emtansine as a second-line treatment. Other treatment options include T-DM1, tucatinib, trastuzumab, and capecitabine, as well as trastuzumab with different chemotherapy partners.
Article
Oncology
Sanja Loeb, Eva Linsmeier, Saskia-Laureen Herbert, Tanja Schlaiss, Matthias Kiesel, Joerg Wischhusen, Jessica Salmen, Peter Kranke, Anne Quenzer, Florian Kurz, Claire Weiss, Elena Gerhard-Hartmann, Achim Woeckel, Joachim Diessner
Summary: The purpose of this study was to investigate the changes in HER2 subtypes between primary breast cancer and recurrent disease. The results showed that HER2 expression increased during the progression of the disease. This information is important for the development of therapeutic options for breast cancer patients.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Rosalynd Upton, Allison Banuelos, Dongdong Feng, Tanuka Biswas, Kevin Kao, Kelly McKenna, Stephen Willingham, Po Yi Ho, Benyamin Rosental, Michal Caspi Tal, Tal Raveh, Jens-Peter Volkmer, Mark D. Pegram, Irving L. Weissman
Summary: Trastuzumab, a targeted anti-HER2 monoclonal antibody, is effective for early-stage HER2(+) breast cancer but resistance often develops in advanced-stage patients. Combining trastuzumab with anti-CD47 immunotherapy shows promising results in inhibiting the growth of ADCC-tolerant HER2(+) breast cancers.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell & Tissue Engineering
Yan Qiu, Libo Yang, Honghong Liu, Xiaobo Luo
Summary: The use of the anti-HER2 drug trastuzumab has significantly improved the prognosis of HER2-positive breast cancer patients, but 50% of patients relapse due to trastuzumab resistance, which is closely related to the presence of breast cancer stem cells (BCSCs). BCSCs are resistant to conventional therapy and may drive distant metastasis and cancer relapse.
Article
Oncology
Chewei Anderson Chang, Jayu Jen, Shaowen Jiang, Azin Sayad, Arvind Singh Mer, Kevin R. Brown, Allison M. L. Nixon, Avantika Dhabaria, Kwan Ho Tang, David Venet, Christos Sotiriou, Jiehui Deng, Kwok-Kin Wong, Sylvia Adams, Peter Meyn, Adriana Heguy, Jane A. Skok, Aristotelis Tsirigos, Beatrix Ueberheide, Jason Moffat, Abhyudai Singh, Benjamin Haibe-Kains, Alireza Khodadadi-Jamayran, Benjamin G. Neel
Summary: Resistance to targeted therapies in HER2-positive breast cancer is often attributed to the presence of drug-tolerant persisters (DTPs). This study reveals that HER2 TKI treatment leads to the emergence of DTPs with different transcriptomes, and these DTPs are originated from pre-DTP cells that cycle stochastically. The findings provide insights into the ontogeny of DTPs and potential vulnerabilities for therapeutic targeting.
Article
Biochemistry & Molecular Biology
Fei Xing, Hongli Gao, Guanglei Chen, Lisha Sun, Jiayi Sun, Xinbo Qiao, Jinqi Xue, Caigang Liu
Summary: This study uncovered the role of CMTM6 in trastuzumab-resistant HER2+ breast cancer. High expression of CMTM6 was associated with worse survival and affected the stability of HER2 protein. These findings suggest CMTM6 as a potential prognostic marker and therapeutic target for overcoming trastuzumab resistance.
Article
Cell Biology
Yujing Li, Yifan Sun, Michael Kulke, Torsten Hechler, Kevin Van der Jeught, Tianhan Dong, Bin He, Kathy D. Miller, Milan Radovich, Bryan P. Schneider, Andreas Pahl, Xinna Zhang, Xiongbin Lu
Summary: The heterozygous loss of chromosome 17p, a common genomic event in breast cancer, leads to global gene expression changes, reduced T cell tumor infiltration, and deletion of tumor suppressor genes like TP53. This loss also makes breast cancer cells sensitive to POLR2A inhibition, enabling targeted precision immunotherapy.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Yoshiya Horimoto, Yumiko Ishizuka, Yuko Ueki, Toru Higuchi, Atsushi Arakawa, Mitsue Saito
Summary: For HER2-positive tumors, there was no difference in disease-free survival between IHC(2+)/FISH(+) tumors and IHC(3+) tumors, but there was a difference in survival after developing metastasis.
Article
Oncology
Maria del Mar Noblejas-Lopez, Cristina Nieto-Jimenez, Eva M. Galan-Moya, David Tebar-Garcia, Juan Carlos Montero, Atanasio Pandiella, Miguel Burgos, Alberto Ocana
Summary: The study demonstrated that the PROTAC compound MZ1 based on BET inhibitors can effectively inhibit the proliferation of HER2+ breast cancer cells, and when combined with trastuzumab, it significantly decreases cell proliferation, formation of three-dimensional structures, and invasiveness, promotes cell apoptosis, and alters apoptosis-related biochemical processes. In vivo studies also showed that the combination treatment of MZ1 and trastuzumab reduced tumor volume in xenografted mice, suggesting a potential novel therapeutic strategy for HER2+ breast cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Anna Adam-Artigues, Enrique J. Arenas, Alex Martinez-Sabadell, Fara Braso-Maristany, Raimundo Cervera, Eduardo Tormo, Cristina Hernando, Maria Teresa Martinez, Juan Carbonell-Asins, Soraya Simon, Jesus Poveda, Santiago Moragon, Sandra Zazo, Debora Martinez, Ana Rovira, Octavio Burgues, Federico Rojo, Joan Albanell, Begona Bermejo, Ana Lluch, Aleix Prat, Joaquin Arribas, Pilar Eroles, Juan Miguel Cejalvo
Summary: AXL overexpression is identified as an essential mechanism of trastuzumab resistance in HER2-positive breast cancer, and targeting AXL can restore trastuzumab response. AXL may serve as a predictive biomarker for prognosis in HER2-positive breast cancer patients. The study emphasizes the importance of targeting AXL in combination with anti-HER2 drugs to overcome resistance.
Review
Oncology
Daniele Galanti, Alessandro Inno, Maria La Vecchia, Nicolo Borsellino, Lorena Incorvaia, Antonio Russo, Stefania Gori
Summary: Brain metastases are often associated with HER2+ breast cancer, and systemic therapy with trastuzumab has been the mainstay. Other HER2-targeted agents have been introduced in clinical practice, with newer agents such as neratinib, tucatinib, and trastuzumab deruxtecan showing interesting activity against brain metastases. Further research is needed to elucidate the optimal sequence of these agents and their combination with local treatment.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Oncology
Melanie Royce, Christy L. Osgood, Anup K. Amatya, Mallorie H. Fiero, C. J. George Chang, Tiffany K. Ricks, Krithika A. Shetty, Jeffrey Kraft, Junshan Qiu, Pengfei Song, Rosane Charlab, Jingyu Yu, Kathryn E. King, Anshu Rastogi, Brian Janelsins, Wendy C. Weinberg, Kathleen Clouse, Vicky Borders-Hemphill, Lindsey Brown, Candace Gomez-Broughton, Zhong Li, Thuy Thanh Nguyen, Zhihao Qiu, Anh-Thy Ly, Suyoung Chang, Tingting Gao, Chi-Ming Tu, Bellinda King-Kallimanis, William F. Pierce, Kelly Chiang, Clara Lee, Kirsten B. Goldberg, John K. Leighton, Shenghui Tang, Richard Pazdur, Julia A. Beaver, Laleh Amiri-Kordestani
Summary: Margetuximab-cmkb in combination with chemotherapy was granted regular FDA approval for the treatment of HER2-positive metastatic breast cancer patients who have received two or more prior anti-HER2 regimens. The SOPHIA study demonstrated that margetuximab had a longer median progression-free survival compared to trastuzumab when both were combined with chemotherapy. Infusion-related reactions were reported as important safety signals associated with margetuximab plus chemotherapy.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Mariano Provencio, Delvys Rodriguez-Abreu, Ana L. Ortega, Gloria Serrano, Carlos Aguado, Fernando Franco, Vanesa Gutierrez, Guillermo Lopez Vivanco, Maria Guirado, Gretel Benitez, Anna Estival, Virginia Calvo, Beatriz Jimenez, Hugo Arasanz, Juan Coves, Margarita Majem, Bartomeu Massuti, Sergio Vazquez, Oscar Juan-Vidal, Ana Collazo-Lorduy, Clara L. Gozalvez, Edel Del Barco, Adriana Rosero, Joaquim Bosch-Barrerra, Maria A. Moreno, Xavier Mielgo-Rubio, Jose C. Villa, Ana Lopez-Martin, Juan F. Cordoba, Francisco de Asis Aparisi, Marta Zafra, Joaquin Mosquera, Javier Perez Altozano, Ernest Nadal, Silvia Catot, Jose Balsalobre, Teresa de Portugal, Paloma Martin, Susana Cuesta de Juan, Manuel Cobo
Summary: A study conducted in 50 Spanish hospitals showed that approximately 8.5% of lung cancer patients had IgG antibodies against SARS-CoV-2 during the first wave of the pandemic, with most still undergoing cancer treatment. When retested around 4.5 months later, 30.8% of patients did not have detectable IgG antibodies.
TRANSLATIONAL LUNG CANCER RESEARCH
(2022)
Article
Chemistry, Medicinal
Joaquim Bosch-Barrera, Ariadna Roque, Eduard Teixidor, Maria Carmen Carmona-Garcia, Aina Arbusa, Joan Brunet, Begona Martin-Castillo, Elisabet Cuyas, Sara Verdura, Javier A. Menendez
Summary: COVID-19 pathophysiology involves respiratory and multiorgan failures caused by dysregulation of the transcription factor STAT3. Treating severe COVID-19 with STAT3 inhibitors like silibinin may hold potential clinical value, as shown in two cancer patients with COVID-19 who experienced significant improvement after receiving oral silibinin.
Article
Biochemistry & Molecular Biology
Monica Cejuela, Begona Martin-Castillo, Javier A. Menendez, Sonia Pernas
Summary: Breast cancer is the most common cancer among women worldwide, and metabolic traits associated with type 2 diabetes such as hyperglycemia, hyperinsulinemia, inflammation, oxidative stress, and obesity are known risk factors. Metformin, a widely prescribed medication for diabetes, has been suggested to have anti-tumor effects based on previous studies. However, recent randomized controlled trials have shown disappointing results, particularly in metastatic breast cancer. This article reviews the mechanisms of action of metformin, discusses past and current clinical trials, and briefly explores future perspectives for incorporating metformin into the prevention and treatment of breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sara Verdura, Jose Antonio Encinar, Salvador Fernandez-Arroyo, Jorge Joven, Elisabet Cuyas, Joaquim Bosch-Barrera, Javier A. Menendez
Summary: This study found that lorlatinib promotes the accumulation of cholesterol and triglycerides in human hepatic cells, and silibinin can reduce the hyperlipidemic effects of lorlatinib. Computational and experimental results also showed that silibinin has a weak inhibitory effect on CYP3A4. These findings suggest that silibinin could be used to reduce the hyperlipidemic activity of lorlatinib in lung cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Elisabet Foguet-Romero, Iris Samarra, Maria Guirro, Marc Riu, Jorge Joven, Javier A. Menendez, Nuria Canela, Antoni DelPino-Rius, Salvador Fernandez-Arroyo, Pol Herrero
Summary: Advances in metabolomics analysis and data treatment have increased our understanding of complex biological systems. Gas chromatography-mass spectrometry (GC-MS) is one of the most commonly used methods. However, method standardization and derivatization steps in GC-MS can introduce experimental errors and be time-consuming. This study proposes the injection-port derivatization (IPD) method to increase analysis throughput.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Nutrition & Dietetics
Angela Llop-Hernandez, Sara Verdura, Elisabet Cuyas, Javier A. Menendez
Summary: This study investigated the survival mechanisms of therapy-induced senescent cells under limited nutrient conditions, identifying key metabolites that support cell survival and observing a correlation between the intensity of pro-inflammatory response induced by different aging-inducing interventions and the compensatory nutritional utilization ability of cells.
Article
Oncology
Sara Verdura, Jose Antonio Encinar, Eduard Teixidor, Antonio Segura-Carretero, Vicente Micol, Elisabet Cuyas, Joaquim Bosch-Barrera, Javier A. Menendez
Summary: This study explores the potential mechanism of resistance of ALK-rearranged NSCLC tumors to ALK-tyrosine kinase inhibitors, driven by epithelial-to-mesenchymal transition (EMT). Chronic exposure to first-generation ALK-TKIs may induce EMT and promote cross-resistance to new-generation ALK-TKIs, but the resistance could be overcome by the EMT inhibitor, silibinin. Silibinin restores the efficacy of new-generation ALK-TKIs by attenuating the TGF beta/SMAD signaling axis in mesenchymal ALK-rearranged NSCLC cells.
Article
Oncology
Elisabet Cuyas, Salvador Fernandez-Arroyo, Sara Verdura, Ruth Lupu, Jorge Joven, Javier A. Menendez
Summary: Epithelial-to-mesenchymal transition (EMT) is a cellular program that enables epithelial cells to transition toward a mesenchymal phenotype with increased cellular motility. It plays a crucial role in embryonic development and tissue repair, but also contributes to the aggressiveness of cancer cells and their resistance to treatment. This study investigates the relationship between metabolic changes and EMT in different types of epithelial cells, providing insights into the progression of cancer and potential therapeutic strategies.
Article
Medicine, General & Internal
Heather Wakelee, Moishe Liberman, Terufumi Kato, Masahiro Tsuboi, Se-Hoon Lee, Shugeng Gao, Ke-Neng Chen, Christophe Dooms, Margarita Majem, Ekkehard Eigendorff, Gaston L. Martinengo, Olivier Bylicki, Delvys Rodriguez-Abreu, Jamie E. E. Chaft, Silvia Novello, Jing Yang, Steven M. M. Keller, Ayman Samkari, Jonathan D. D. Spicer
Summary: Among patients with resectable early-stage NSCLC, perioperative pembrolizumab improved event-free survival, major pathological response, and pathological complete response. The addition of pembrolizumab to neoadjuvant chemotherapy followed by surgery showed significant benefits compared to neoadjuvant chemotherapy alone followed by surgery.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Mariano Provencio, Anna Estival, Fernando Franco, Guillermo Lopez-Vivanco, Maria Saigi, Hugo Arasanz, Pilar Diz, Enric Carcereny, Javier Garcia, Carlos Aguado, Joaquin Mosquera, Eluska Iruarrizaga, Margarita Majem, Joaquim Bosch-Barrera, Xavier Mielgo-Rubio, Maria Guirado, Oscar Juan-Vidal, Ana Blasco, Clara Lucia Goz, Anabel Del Barrio, Teresa De Portugal, Ana Lopez-Martin, Gloria Serrano, Begona Campos, Judit Rubio, Silvia Catot, Beatriz Esteban, Juan Luis Marti-Ciriquian, Edel del Barco
Summary: Lung cancer patients can safely and effectively generate an immune response against SARS-CoV-2 after full vaccination, regardless of the cancer treatment received. The use of immunotherapy or oral targeted therapy and administration of the mRNA-1273 vaccine were associated with an increased likelihood of seropositivity.
Article
Medicine, General & Internal
Mariano Provencio, Ernest Nadal, Jose L. Gonzalez-Larriba, Alex Martinez-Marti, Reyes Bernabe, Joaquim Bosch-Barrera, Joaquin Casal-Rubio, Virginia Calvo, Amelia Insa, Santiago Ponce, Noemi Reguart, Javier de Castro, Joaquin Mosquera, Manuel Cobo, Andres Aguilar, Guillermo Lopez Vivanco, Carlos Camps, Rafael Lopez-Castro, Teresa Moran, Isidoro Barneto, Delvys Rodriguez-Abreu, Roberto Serna-Blasco, Raquel Benitez, Carlos Aguado de la Rosa, Ramon Palmero, Florentino Hernando-Trancho, Javier Martin-Lopez, Alberto Cruz-Bermudez, Bartomeu Massuti, Atocha Romero
Summary: This study evaluated the efficacy of the neoadjuvant nivolumab plus chemotherapy regimen on operable stage III non-small-cell lung cancer (NSCLC) patients. The results showed that patients receiving the combination therapy had a higher rate of pathological complete response and longer survival, indicating the effectiveness of this treatment approach in this patient population.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Cell Biology
Elisabet Cuyas, Sara Verdura, Begona Martin-Castillo, Javier A. Menendez
Summary: MOTS-c is an exercise-mimetic peptide expressed in multiple tissues and can be detected as a circulating hormone in the blood. Its mechanisms of action involve insulin sensitization, enhanced glucose utilization, suppression of mitochondrial respiration, and targeting of the folate-AICAR-AMPK pathway. The regulatory actions of the anti-diabetic drug metformin on MOTS-c have not been evaluated in detail.
Article
Oncology
Lin Yang, Travis Vander Steen, Ingrid Espinoza, Elisabet Cuyas, Sara Verdura, Javier A. Menendez, Ruth Lupu
Summary: This study reveals the nuclear translocation mechanism of HRG in breast cancer and suggests that nuclear HRG has different functions and effects from extracellular HRG, providing a new paradigm for the functional and therapeutic research of nuclear HRG in breast cancer.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
Ingrid Espinoza, Chandra Kurapaty, Cheol-Hong Park, Travis Vander Steen, Celina G. Kleer, Elizabeth Wiley, Alfred Rademaker, Elisabet Cuyas, Sara Verdura, Maria Buxo, Carol Reynolds, Javier A. Menendez, Ruth Lupu
Summary: Triple-negative/basal-like breast cancer is characterized by aggressive biological features. Targeting CCN1/CYR61 may have therapeutic value in suppressing the biological aggressiveness of this type of breast cancer.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)