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.
Review
Multidisciplinary Sciences
Ye Yuan, Xumei Liu, Yi Cai, Wenyuan Li
Summary: According to this study, pyrotinib combined with chemotherapy is more effective than lapatinib combined with chemotherapy in terms of PFS and ORR for patients with HER2-positive metastatic breast cancer, but it carries higher safety risks.
Review
Oncology
Roberta Caputo, Giuseppe Buono, Vincenzo Di Lauro, Daniela Cianniello, Claudia Von Arx, Matilde Pensabene, Martina Pagliuca, Carmen Pacilio, Francesca Di Rella, Annarita Verrazzo, Claudia Martinelli, Francesco Nuzzo, Michelino De Laurentiis
Summary: Neratinib, used after adjuvant trastuzumab therapy, significantly improves disease-free survival in early-stage HER2+ breast cancer without increased risk of long-term toxicity. Diarrhea, the most common adverse event associated with neratinib, can be managed with dose-escalation and prophylactic strategies, allowing treatment continuation.
Review
Oncology
Kreina Sharela Vega Cano, David Humberto Marmolejo Castaneda, Santiago Escriva-de-Romani, Cristina Saura
Summary: Therapeutic advances have significantly improved the natural history of HER2-positive metastatic breast cancer. Double anti-HER2 blockade with a taxane is currently the best option in first-line, but T-DXd has emerged as the new standard in second-line. New treatments and combinations are being developed to address resistance and progress in these patients.
Article
Oncology
Stephanie N. Shishido, Rahul Masson, Liya Xu, Lisa Welter, Rishvanth Kaliappan Prabakar, Anishka D'Souza, Darcy Spicer, Irene Kang, Priya Jayachandran, James Hicks, Janice Lu, Peter Kuhn
Summary: Metastatic breast cancer (mBC) patients have a high risk of progression and poor prognosis. Liquid biopsy, particularly the analysis of cell-free DNA (cfDNA) and single circulating tumor cells (CTCs), can provide valuable clinical information for ERBB2 mutant, non-amplified mBC patients, guiding personalized oncology.
Review
Chemistry, Medicinal
Giovanna Chila, Vincenzo Guarini, Danilo Galizia, Elena Geuna, Filippo Montemurro
Summary: Neratinib is a valuable therapeutic option for metastatic, HER2-positive breast cancer, particularly in cases of trastuzumab-resistant disease. Although it has shown positive effects on progression-free survival and response duration, it did not confer an overall survival benefit or improvement in quality of life in the NALA trial.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Oncology
Ana Carla Castro-Guijarro, Angel Matias Sanchez, Marina Ines Flamini, Christoph F. A. Vogel
Summary: This study aims to identify biomarkers for predicting disease progression and therapy efficacy in HER2-positive breast cancer, as well as to overcome resistance. Combining anti-HER2 therapies shows potential in inhibiting cell adhesion and migration critical for cancer metastasis. Deregulated proteins in resistant cells may serve as potential biomarkers of therapy response and resistance. These findings are promising for personalized breast cancer management to maximize the safety and efficacy of anti-HER2 therapies.
Article
Oncology
Chenchen Ji, Feng Li, Yang Yuan, Huiqiang Zhang, Li Bian, Shaohua Zhang, Tao Wang, Jianbin Li, Zefei Jiang
Summary: This study compared the efficacy and safety between novel anti-human epidermal growth factor receptor 2 antibody-drug conjugates (ADCs) and trastuzumab emtansine for patients with tyrosine kinase inhibitor (TKI) treatment failure. The results showed that both T-Dxd and other novel anti-HER2 ADCs had significantly better progression-free survival and objective response rate than T-DM1, with tolerable toxicities.
Article
Oncology
Niamh Cunningham, Scott Shepherd, Kabir Mohammed, Karla A. Lee, Mark Allen, Stephen Johnston, Emma Kipps, Sophie McGrath, Jillian Noble, Marina Parton, Alistair Ring, Nicholas C. Turner, Alicia F. C. Okines
Summary: This study describes the tolerability and efficacy of neratinib as a monotherapy and in combination with capecitabine in advanced HER2-positive breast cancer. The results showed that neratinib was effective in both patients with and without brain metastases, with similar progression-free survival and overall survival rates as previous trials. Diarrhea was the most common adverse event but could be managed with prophylaxis. Routine anti-diarrheal prophylaxis allows this combination therapy to be safely delivered to patients in a real-world setting.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Article
Oncology
Jamunarani Veeraraghavan, Carolina Gutierrez, Vidyalakshmi Sethunath, Sepideh Mehravaran, Mario Giuliano, Martin J. Shea, Tamika Mitchell, Tao Wang, Sarmistha Nanda, Resel Pereira, Robert Davis, Kristina Goutsouliak, Lanfang Qin, Carmine De Angelis, Irmina Diala, Alshad S. Lalani, Chandandeep Nagi, Susan G. Hilsenbeck, Mothaffar F. Rimawi, C. Kent Osborne, Rachel Schiff
Summary: The combination of neratinib and trastuzumab showed better efficacy in HER2+ breast cancer compared to pertuzumab plus trastuzumab or lapatinib plus trastuzumab. This combination treatment also accelerated complete response. Further clinical testing is warranted to evaluate the efficacy of neratinib plus trastuzumab with or without chemotherapy in the neoadjuvant setting for HER2+ breast cancer.
Article
Oncology
Guilherme Nader-Marta, Veronique Debien, Daniel Eiger, Zoi Tsourti, Rafael Caparica, Marie Kassapian, Sylvia Napoleone, Susanne Hultsch, Larissa Korde, Yingbo Wang, Saranya Chumsri, Kathleen Pritchard, Michael Untch, Meritxell Bellet-Ezquerra, Daniela Dornelles Rosa, Alvaro Moreno-Aspitia, Martine Piccart, Urania Dafni, Evandro de Azambuja
Summary: The sub-analysis of the ALTTO trial demonstrates that patients with small node-negative breast cancer treated with trastuzumab and concomitant chemotherapy have excellent long-term outcomes.
BRITISH JOURNAL OF CANCER
(2022)
Review
Pharmacology & Pharmacy
Desh Deepak Singh, Hae-Jeung Lee, Dharmendra Kumar Yadav
Summary: Breast cancer is a heterogeneous disease caused by epigenetic modifications and genetic heterogeneity. HER2+ breast cancer is a more aggressive subtype with difficult diagnosis and prognosis. Various targeted therapies have been developed, but drug resistance and limited efficacy remain challenges. Nano formulations show potential in the treatment of HER2+ breast cancer.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Zihong Wu, Jiamei Wang, Fengming You, Xueke Li, Chong Xiao
Summary: HER2-positive metastatic breast cancer is the leading cause of cancer death in women, and there is currently no optimal line of therapy after multiple treatment failures. Clinical trials have shown that treatment with irreversible pan-HER tyrosine kinase inhibitors in combination with chemotherapy significantly improves survival outcomes. Available findings suggest that irreversible pan-HER tyrosine kinase inhibitors, such as pyrotinib and neratinib, in combination with chemotherapy, may represent a beneficial salvage therapy for patients with HER2-positive metastatic breast cancer.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Jingru Qiu, Qinghong Liu, Peixia Li, Qiaoyun Jiang, Weijia Chen, Donghai Li, Guiling Li, Gang Shan
Summary: This work presents a photocatalytic approach called ligand-directed photodegradation of interacting proteins (LDPIP) for efficient degradation of protein-protein heterodimers. LDPIP utilizes a photosensitizing protein ligand, appropriate light, and molecular oxygen to induce oxidative damage to both the ligand-binding protein and its interacting protein partner. As a showcase study, a photosensitizing HER2 ligand HER-PS-I was designed based on the FDA-approved HER2 inhibitor lapatinib to degrade HER2 and its difficult-to-target interacting protein partner HER3. HER-PS-I exhibited excellent anticancer activity in drug-resistant MDA-MB-453 cells and multicellular spheroids. The LDPIP approach holds promise for degrading undruggable or difficult-to-drug proteins.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Cancan Lyu, Yuanchao Ye, Maddison M. Lensing, Kay-Uwe Wagner, Ronald J. Weigel, Songhai Chen
Summary: In HER2(+) breast cancer, overactivation of HER2 leads to aberrant G(i/o)-GPCR signaling, promoting cancer progression and resistance to HER2-targeted therapy. Pharmacologically deactivating GPCR signaling can block tumor growth and enhance therapeutic efficacy.
Article
Medicine, General & Internal
Sivisan Suntheralingam, Chun-Po Steve Fan, Oscar Calvillo-Arguelles, Husam Abdel-Qadir, Eitan Amir, Paaladinesh Thavendiranathan
Summary: This retrospective cohort study assessed the performance of three published risk prediction models in identifying the risk of Cancer-therapeutics-related cardiac dysfunction (CTRCD) during or immediately post treatment with trastuzumab therapy for HER2+ breast cancer. The results showed that these models can identify relative differences in CTRCD risk, but their ability to predict absolute risk is limited.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Oncology
Elena Diaz-Rodriguez, Lucia Gandullo-Sanchez, Alberto Ocana, Atanasio Pandiella
Summary: A proportion of breast tumors carry the oncogenic HER2 protein, and while therapies targeting HER2 have shown efficacy, resistance remains a significant clinical issue. The emergence of antibody-drug conjugates (ADCs) has provided a new category of antitumor agents for HER2+ breast tumors. With two FDA-approved anti-HER2 ADCs in clinical use and others in development, there is hope for improving outcomes and overcoming resistance in HER2-positive breast cancer patients.
Article
Biochemistry & Molecular Biology
Maria del Mar Noblejas-Lopez, Lucia Gandullo-Sanchez, Eva M. Galan-Moya, Raquel Lopez-Rosa, David Tebar-Garcia, Cristina Nieto-Jimenez, Monica Gomez-Juarez, Miguel Burgos, Atanasio Pandiella, Alberto Ocana
Summary: This article explores the antitumoral activity of a novel compound against CDK9 in breast cancer cells, showing significant inhibitory effects in certain subtypes and particular sensitivity in trastuzumab-resistant cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Laith Al-Showbaki, Fahad A. Almugbel, Husam A. Alqaisi, Eitan Amir, Eric X. Chen
Summary: Most published RCTs evaluating PD-1/PD-L1 targeting mAbs did not achieve the hypothesized benefits. The optimism bias needs attention in cancer clinical research community, considering the number of these agents in development.
Article
Pharmacology & Pharmacy
Carmen Moya-Lopez, Alberto Juan, Murillo Donizeti, Jesus Valcarcel, Jose A. Vazquez, Eduardo Solano, David Chapron, Patrice Bourson, Ivan Bravo, Carlos Alonso-Moreno, Pilar Clemente-Casares, Carlos Gracia-Fernandez, Alessandro Longo, Georges Salloum-Abou-Jaoude, Alberto Ocana, Manuel M. Pineiro, Carolina Hermida-Merino, Daniel Hermida-Merino
Summary: A series of bionanocomposites composed of shark gelatin hydrogels and PLA nanoparticles with different nanostructures were designed for personalized treatment approaches. The systems were customized for drug release, ease of storage and local administration, biocompatibility, and cell growth capability at the biomolecular level. The study successfully formulated nanoparticles with different antitumoral compounds and characterized the bionanocomposites using various techniques. The drug release profiles were analyzed and correlated to the nanostructure of the drug delivery system.
Article
Oncology
A. Desnoyers, M. Nadler, B. E. Wilson, S. Stajer, E. Amir
Summary: PARP inhibitors have modest antitumor activity in advanced breast cancer, and their efficacy may vary based on patient and tumor characteristics. Combination with platinum-based chemotherapy improves objective response rate, while lower response is observed with PARP inhibitors as monotherapy after platinum exposure. PARP inhibitors demonstrate improved progression-free survival compared to standard chemotherapy, but no significant difference in overall survival. There is no association between BRCA mutations and objective response rate.
Article
Multidisciplinary Sciences
Roman Adam, Ariadna Tibau, Consolacion Molto Valiente, Bostjan Seruga, Alberto Ocana, Eitan Amir, Arnoud J. Templeton
Summary: Only around half of the recently approved cancer drugs in Switzerland meet the criteria for substantial clinical benefit, and there is at best only moderate concordance between the grading systems.
Article
Oncology
Alberto Juan, Maria del Mar Noblejas-Lopez, Ivan Bravo, Maria Arenas-Moreira, Cristina Blasco-Navarro, Pilar Clemente-Casares, Agustin Lara-Sanchez, Atanasio Pandiella, Carlos Alonso-Moreno, Alberto Ocana
Summary: The encapsulation of PARPi olaparib and BET inhibitor JQ1 into nanoparticles has shown potential preclinical benefits in the treatment of BRCAness tumors. This combination therapy can overcome PARPi resistance and enhance the efficacy of PARPi.
Review
Oncology
Abhenil Mittal, Faris Tamimi, Consolacion Molto, Nicholas Meti, Laith Al-Showbaki, Brooke E. Wilson, Eitan Amir
Summary: The study reveals that the 3-year disease-free survival (DFS) for breast cancer patients with residual disease (RD) has improved over time, possibly due to dual HER2 targeted therapy.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2023)
Review
Oncology
Laith Al-Showbaki, Brooke Wilson, Faris Tamimi, Consolacion Molto, Abhenil Mittal, David W. Cescon, Eitan Amir
Summary: This study explores the impact of immune checkpoint inhibitors (ICIs) on circulating tumor DNA (ctDNA) levels. A meta-analysis of 18 clinical trials reveals that a reduction in ctDNA levels during treatment is associated with significant improvements in progression-free survival (PFS) and overall survival (OS).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Lucia Paniagua-Herranz, Bernard Doger, Cristina Diaz-Tejeiro, Adrian Sanvicente, Cristina Nieto-Jimenez, Victor Moreno, Pedro Perez Segura, Balazs Gyorffy, Emiliano Calvo, Alberto Ocana
Summary: This study explored the high expression of EGFR and MET in prostate adenocarcinoma and pancreatic adenocarcinoma, and found that it was related to high expression of PD-L1, suggesting the potential for future combination therapy using bi-specific EGFR/MET antibodies and anti-PD(L)1 inhibitors.
Article
Engineering, Biomedical
Christian Rafael Quijia, Geovana Navegante, Rafael Miguel Sabio, Valeria Valente, Alberto Ocana, Carlos Alonso-Moreno, Regina Celia Galvao Frem, Marlus Chorilli
Summary: Researchers synthesized a nanomaterial MM@PIP@MIL-100(Fe) that has potential anti-breast cancer activity by encapsulating Piperine (PIP). The nanomaterial exhibited higher cytotoxicity in breast cancer cell lines compared to free PIP, indicating its potential as an effective treatment for breast cancer.
JOURNAL OF FUNCTIONAL BIOMATERIALS
(2023)
Review
Oncology
Abhenil Mittal, Consolacion Molto Valiente, Faris Tamimi, Massimo Di Iorio, Laith Al-Showbaki, David W. Cescon, Eitan Amir
Summary: The presence of ctDNA is prognostic in solid tumors, but there is variability in study results, leading to uncertainty about its clinical validity. Adequately designed clinical trials are needed to demonstrate its clinical utility.
JNCI CANCER SPECTRUM
(2023)
Review
Oncology
Cristina Nieto-Jimenez, Adrian Sanvicente, Cristina Diaz-Tejeiro, Victor Moreno, Alfonso Lopez de Sa, Emiliano Calvo, Joaquin Martinez-Lopez, Pedro Perez-Segura, Alberto Ocana
Summary: ADCs have shown clinical activity in various indications, with TATs for haematological malignancies being more specific than those for solid tumors. There are unexplored niche indications for ADCs in solid tumors, and some TATs are essential for the survival of tumor cells like CD71, PSMA, and PTK7.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Esther Cabanas Morafraile, Cristina Saiz-Ladera, Cristina Nieto-Jimenez, Balazs Gyorffy, Adam Nagy, Guillermo Velasco, Pedro Perez-Segura, Alberto Ocana
Summary: This study describes a novel therapeutic strategy for treating colorectal cancer (CRC) patients with BRAF mutations. By identifying upregulated proteins on the surface of tumor cells as treatment targets and observing the transcriptional profile associated with antigen presenting cells, it is suggested that a combination of anti PD(L)1 with other co-inhibitor receptors can be explored for treating BRAF-mutated CRC patients.
Review
Oncology
Albrecht Stenzinger, Arndt Vogel, Ulrich Lehmann, Angela Lamarca, Paul Hofman, Luigi Terracciano, Nicola Normanno
Summary: Cholangiocarcinomas are a heterogeneous group of tumors with distinct genomic alterations. Next-generation sequencing is a powerful tool for identifying gene variants and guiding personalized treatment for patients with cholangiocarcinomas. Understanding the use of NGS in molecular profiling is crucial for healthcare professionals to optimize treatment outcomes.
CANCER TREATMENT REVIEWS
(2024)
