Review
Biochemistry & Molecular Biology
Rosalin Mishra, Hima Patel, Samar Alanazi, Mary Kate Kilroy, Joan T. Garrett
Summary: The PI3K pathway is crucial in cancer development and is a promising therapeutic target. Clinical trials are ongoing to evaluate the efficacy and potential risks associated with PI3K inhibitors in overcoming resistance to current therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Shijie Wei, Yubao Zhang, Xiaoran Ma, Yan Yao, Qinqin Zhou, Wenfeng Zhang, Chao Zhou, Jing Zhuang
Summary: This study reveals that matrine, an alkaloid from the medicinal plant Sophora flavescens, has strong anticancer effects and can be explored as a new therapeutic agent for triple-negative breast cancer (TNBC). Through bioinformatics analysis and network pharmacology, researchers found that matrine inhibits the PI3K/AKT pathway, suppresses cell proliferation and invasion, induces apoptosis and autophagy, effectively inhibiting the growth and spread of TNBC.
SCIENTIFIC REPORTS
(2023)
Article
Biology
Floyd Hassenrueck, Maria Farina-Morillas, Lars Neumann, Francesco Landini, Stuart James Blakemore, Mina Rabipour, Juan Raul Alvarez-Idaboy, Christian P. Pallasch, Michael Hallek, Rocio Rebollido-Rios, Guenter Krause
Summary: Cell-based and molecular exploration provides comparative characterization of currently developed PI3K inhibitors and structural insights for future inhibitor design. The study focuses on targeting the PI3K isoform p110 delta against B cell malignancies and evaluates the potency, isoform-selectivity, and molecular interactions of various PI3Ki chemotypes. The I777M substitution affects the efficacy and selectivity of p110 delta-selective inhibitors, but not multi-targeted inhibitors, due to its effect on the conformational flexibility of p110 delta's specificity or affinity pockets. This research provides valuable information for optimizing PI3Ki design.
COMMUNICATIONS BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Sushmita Mustafi, Vladimir Camarena, Rehana Qureshi, David W. Sant, Zachary Wilkes, Daniel Bilbao, Joyce Slingerland, Susan B. Kesmodel, Gaofeng Wang
Summary: The study demonstrated that vitamin C can synergistically enhance the anti-cancer effects of buparlisib in treating PIK3CA-mutated triple negative breast cancer cells, leading to reduced dosage requirements and potential mitigation of dose-dependent side effects. Vitamin C modulates PI3K pathway gene expression, inhibits AKT phosphorylation, and works in coordination with buparlisib to inhibit cancer cell growth.
Review
Oncology
Silvia Rita Vitale, Federica Martorana, Stefania Stella, Gianmarco Motta, Nicola Inzerilli, Michele Massimino, Elena Tirro, Livia Manzella, Paolo Vigneri
Summary: The PI3K pathway is commonly deregulated in breast cancer, leading to resistance to inhibitors. Mechanisms of resistance include PI3K alterations, pathway reactivation, and enhancement of survival pathways.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alexandra M. Simond, Tung Bui, Dongmei Zuo, Virginie Sanguin-Gendreau, Trisha Rao, Wayne A. Phillips, Robert D. Cardiff, William J. Muller
Summary: This study found that the p110 alpha(HR) mutation attenuates metastatic behavior and is associated with the formation of ductal carcinoma in situ (DCIS) in ErbB2-driven breast cancer.
Article
Agriculture, Dairy & Animal Science
Soo-Hyeon Kim, Byung-Joon Seung, Seung-Hee Cho, Ha-Young Lim, Min-Kyung Bae, Jung-Hyang Sur
Summary: The frequency of PIK3CA H1047R mutation in canine mammary tumors is 14.3%, leading to dysregulation of downstream molecules Akt2, p-Akt, and PTEN, with the exception of a higher level of PTEN in mutated tumors. No significant correlation was found between PIK3CA H1047R mutation and expression of downstream molecules, suggesting the dysregulation of components in the PI3K/Akt/PTEN pathway is a feature in canine mammary tumors distinct from the mutation.
Review
Oncology
Paola Fuso, Margherita Muratore, Tatiana D'Angelo, Ida Paris, Luisa Carbognin, Giordana Tiberi, Francesco Pavese, Simona Duranti, Armando Orlandi, Giampaolo Tortora, Giovanni Scambia, Alessandra Fabi
Summary: This article reviews the molecular aberrations in the PI3K pathway in breast cancer and its potential as a therapeutic target. Various PI3K inhibitors have been developed and clinical trials have been conducted to improve the treatment outcome of metastatic breast cancer. However, further research is needed to discover other actionable genetic alterations for personalized and precision medicine.
Review
Biochemistry & Molecular Biology
Qiyun Shi, Juncheng Xuhong, Hao Tian, Man Qu, Yi Zhang, Jun Jiang, Xiaowei Qi
Summary: This systematic review and meta-analysis study examines the predictive and prognostic value of PIK3CA mutations in HER2-positive breast cancer treated with TKIs. The analysis of 17 studies involving 1706 patients shows that wild-type PIK3CA patients had higher complete response rates and objective response rates compared to mutated PIK3CA patients. Additionally, PIK3CA mutations were marginally associated with poorer progression-free survival and overall survival in metastatic breast cancer patients. Therefore, PIK3CA mutations can predict treatment response in HER2-positive breast cancer patients treated with TKI-containing regimens.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Oncology
Wei-Pang Chung, Wei-Lun Huang, Chun-Hui Lee, Hui-Ping Hsu, Wan-Ling Huang, You-Yu Liu, Wu-Chou Su
Summary: The activation of the PI3K signaling pathway is associated with the development and resistance of breast cancer. Mutations in PIK3CA and loss of PTEN occur in all subtypes of breast cancer. The combination of PI3K inhibitors and trastuzumab shows potential in treating HER2-positive breast cancer, but its effectiveness in HER2-positive breast cancer with PIK3CA mutations and/or PTEN loss is still unclear. In this study, a novel alpha isoform-specific PI3K inhibitor was shown to effectively target breast cancer cells with PIK3CA mutations or PTEN deficiency when combined with trastuzumab. The combination therapy was found to be ineffective in breast cancer cells without PI3K pathway alterations, indicating a biomarker-specific treatment. In vivo testing in a mouse model confirmed the efficacy of the combination therapy in reducing tumor volume. This cytotoxic chemotherapy-free regimen, as a biomarker-driven strategy, warrants further investigation for the treatment of HER2-positive breast cancer.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Oncology
Lin Shi, Jinying Lu, Da Zhong, Meijuan Song, Jian Liu, Wenhua You, Wen-Hui Li, Lin Lin, Dongyan Shi, Yun Chen
Summary: Mucosal-associated invariant T (MAIT) cells in non-small cell lung cancer (NSCLC) patients exhibit an exhausted tumor-promoting phenotype and the subset of circulating MAIT cells can predict the response to anti-PD-1 immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Niamh M. Keegan, Simon J. Furney, Janice M. Walshe, Giuseppe Gullo, M. John Kennedy, Diarmuid Smith, John McCaffrey, Catherine M. Kelly, Keith Egan, Jennifer Kerr, Mark Given, Peter O'Donovan, Andres Hernando, Ausra Teiserskiene, Imelda Parker, Elaine Kay, Angela Farrelly, Aoife Carr, Giulio Calzaferri, Ray McDermott, Maccon M. Keane, Liam Grogan, Oscar Breathnach, Patrick G. Morris, Sinead Toomey, Bryan T. Hennessy
Summary: This study highlighted the significance of PIK3CA gene in HER2 positive breast cancer and investigated the clinical activity of combination therapy with the PI3K inhibitor copanlisib and trastuzumab in breast cancer patients.
Review
Oncology
Nicola Fusco, Umberto Malapelle, Matteo Fassan, Caterina Marchio, Simonetta Buglioni, Simonetta Zupo, Carmen Criscitiello, Paolo Vigneri, Angelo Paolo Dei Tos, Eugenio Maiorano, Giuseppe Viale
Summary: Despite advances in diagnosis and treatment of metastatic breast cancer (MBC), it remains largely incurable. Pharmacologic targeting of PIK3CA in HR+/HER2(-) MBC has shown significant benefits, and tailored patient selection is crucial for optimal outcomes. Clinical relevant PIK3CA alterations can be detected in various biospecimens using different techniques, guiding appropriate clinical management.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, General & Internal
Joseph S. Reddy, Jiangli Jin, Sarah J. Lincoln, Charlotte C. G. Ho, Julia E. Crook, Xue Wang, Kimberly G. Malphrus, Thuy Nguyen, Nikoleta Tamvaka, Maria T. Greig-Custo, John A. Lucas, Neill R. Graff-Radford, Nilufer Ertekin-Taner, Minerva M. Carrasquillo
Summary: This study aims to investigate the genetic risk factors and plasma biomarkers for Alzheimer's disease (AD) in African Americans (AA) through gene expression and genetic polymorphism analysis. The results showed that plasma levels of CLU, ABCA7, AKAP9, and other genes were associated with the risk of AD. Incorporating plasma mRNA levels may improve the predictive value of AD biomarker panels.
Article
Oncology
Masayuki Sato, Yukihiro Umeda, Tetsuya Tsujikawa, Tetsuya Mori, Miwa Morikawa, Masaki Anzai, Yuko Waseda, Maiko Kadowaki, Yasushi Kiyono, Hidehiko Okazawa, Tamotsu Ishizuka
Summary: Changes in F-18-FLT PET parameters may serve as an early predictive biomarker for the response to anti-PD-1 therapy in NSCLC patients, but pseudoprogression should be noted in imaging at 2 weeks after treatment initiation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Nuria Chic, Stephen J. Luen, Paolo Nuciforo, Roberto Salgado, Debora Fumagalli, Florentine Hilbers, Yingbo Wang, Evandro de Azambuja, Istvan Lang, Serena Di Cosimo, Cristina Saura, Jens Huober, Aleix Prat, Sherene Loi
Summary: The CelTIL score has been identified as a promising biomarker in early-stage HER2-positive breast cancer, showing potential to guide the escalation or deescalation of systemic therapy.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Review
Pharmacology & Pharmacy
Elisa Agostinetto, Agnese Losurdo, Guilherme Nader-Marta, Armando Santoro, Kevin Punie, Romualdo Barroso, Lazar Popovic, Cinzia Solinas, Marleen Kok, Evandro de Azambuja, Matteo Lambertini
Summary: This review focuses on the use of immunotherapeutic strategies in triple negative breast cancer (TNBC), discussing evidence from early and advanced TNBC and novel immunomodulatory approaches. PD-1 blockade has been approved for TNBC treatment, but challenges include predictive biomarker identification and balancing efficacy with toxicity. Evaluation of treatment combinations and new immunotherapeutic strategies beyond PD-1 blockade is ongoing.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2022)
Article
Oncology
Chau Dang, Michael S. Ewer, Suzette Delaloge, Jean-Marc Ferrero, Ramon Colomer, Luis de la Cruz-Merino, Theresa L. Werner, Katherine Dadswell, Mark Verrill, Daniel Eiger, Sriparna Sarkar, Sanne Lysbet de Haas, Eleonora Restuccia, Sandra M. Swain
Summary: The BERENICE study assessed the cardiac safety of neoadjuvant-adjuvant therapy for high-risk, HER2-positive early breast cancer. The study confirmed that pertuzumab-trastuzumab-based therapies are the standard of care for this patient population, with no new cardiac issues reported.
Review
Oncology
G. Nader-Marta, D. Martins-Branco, E. Agostinetto, M. Bruzzone, M. Ceppi, L. Danielli, M. Lambertini, N. Kotecki, A. Awada, E. de Azambuja
Summary: This study assessed the clinical outcomes of HER2-positive metastatic breast cancer (MBC) patients with brain metastases (BMs) treated with tyrosine kinase inhibitor (TKI)-containing regimens compared to non-TKI-containing regimens. The results showed a trend favoring TKI-containing regimens in terms of progression-free survival (PFS) in patients with BM. Sensitivity analysis including trials evaluating tucatinib, lapatinib, or pyrotinib regimens demonstrated a significant PFS benefit in patients with BM.
Review
Oncology
Diogo Martins-Branco, Guilherme Nader-Marta, Ana Tecic Vuger, Veronique Debien, Lieveke Ameye, Mariana Brandao, Kevin Punie, Angela Loizidou, Karen Willard-Gallo, Chloe Spilleboudt, Ahmad Awada, Martine Piccart, Evandro de Azambuja
Summary: This systematic review and meta-analysis evaluated the immune response to anti-SARS-CoV-2 vaccination in cancer patients. The results showed that cancer patients had sustained humoral and adaptive immune responses for at least 2 months after complete prime-vaccination. However, patients with hematological malignancies had lower immune responses.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Oncology
Bolivar Arboleda, Rupert Bartsch, Evandro de Azambuja, Erika Hamilton, Nadia Harbeck, Jennifer Klemp, Michael Knauer, Sherko Kuemmel, Reshma Mahtani, Lee Schwartzberg, Cynthia Villarreal-Garza, Antonio Wolff
Summary: This article summarizes the key results of an expert panel discussion on optimizing ovarian function suppression for premenopausal women with HR+, HER2- early breast cancer. The panel suggests that combining chemotherapy with ovarian function suppression may result in better treatment outcomes and avoid adverse effects associated with adjuvant chemotherapy.
Review
Oncology
Chiara Molinelli, Flavia Jacobs, Caterina Marchio, Francesca Pitto, Maurizio Cosso, Stefano Spinaci, Evandro de Azambuja, Francesco Schettini, Elisa Agostinetto, Matteo Lambertini
Summary: There has been significant progress in the research of HER2-low breast cancer in recent years, with evidence showing that patients with this subtype can also benefit from anti-HER2 therapies. However, there are still important issues that need further investigation, including the accurate assessment of HER2-low status, clarification of its prognostic implications, and global access to newly approved drugs. This field holds great potential in providing effective personalized treatment strategies for a wider range of patients.
Article
Oncology
Karin Jordan, Evandro De Azambuja, Teresa Amaral, Michiel Strijbos, Giuseppe Curigliano, Florian Lordick
Summary: High-quality medical oncology education is crucial for medical oncologists to provide excellent care for cancer patients. The demand for such education is increasing due to the development of new therapies and the rising number of cancer patients. Access to medical oncology education varies across countries. The European Society for Medical Oncology and other associations have implemented initiatives, such as the ESMO/ASCO global curriculum, to promote access to high-quality education.
ONCOLOGY RESEARCH AND TREATMENT
(2023)
Review
Oncology
Elisa Agostinetto, Flavia Jacobs, Veronique Debien, Alex De Caluwe, Catalin-Florin Pop, Xavier Catteau, Philippe Aftimos, Evandro de Azambuja, Laurence Buisseret
Summary: Treatment strategies for early breast cancer have significantly improved, with the development of new drugs and treatment methods. Pre-surgical treatment and post-neoadjuvant treatment have become the focus of research, allowing direct evaluation of treatment effects and risk stratification. Approved post-neoadjuvant treatments include T-DM1, capecitabine, immune checkpoint inhibitors, PARP inhibitors, and CDK 4/6 inhibitors.
Editorial Material
Oncology
Elisa Agostinetto, Evandro de Azambuja, Matteo Lambertini
Article
Oncology
Mariana Brandao, Diogo Martins-Branco, Claudia De Angelis, Peter Vuylsteke, Richard D. Gelber, Nancy Van Damme, Lien van Walle, Arlindo R. Ferreira, Matteo Lambertini, Francesca Poggio, Didier Verhoeven, Annelore Barbeaux, Francois P. Duhoux, Hans Wildiers, Carmela Caballero, Ahmad Awada, Martine Piccart-Gebhart, Kevin Punie, Evandro de Azambuja
Summary: Among patients with de novo metastatic breast cancer who received systemic treatment and survived for nine months or more, those who underwent surgery of the primary tumor within nine months of diagnosis had longer overall survival compared to those who did not.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Oncology
Diogo Martins-Branco, Marie Kassapian, Veronique Debien, Rafael Caparica, Daniel Eiger, Urania Dafni, Charitini Andriakopoulou, Sarra El-Abed, Susan L. Ellard, Miguel Izquierdo, Malou Vicente, Saranya Chumsri, Martine Piccart-Gebhart, Alvaro Moreno-Aspitia, Ann Soegaard Knop, Janine Lombard, Evandro de Azambuja
Summary: This study aimed to assess the impact of erythropoiesis-stimulating agents (ESA) on the outcomes of patients with HER2-positive early breast cancer (EBC). The results showed that ESA administration did not have a negative impact on disease-free survival and overall survival, and the incidence of adverse events was low in patients receiving ESA treatment.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Respiratory System
Anouk Goudsmit, Mariana Brandao, Ali Oullai, Dan Engelman, Nathalie Ghorra, Tarik Daif, Tom Buelens, Anne-Pascale Meert
Summary: This case report presents a patient with lung adenocarcinoma who developed optic neuritis with positive CRMP-5 IgG after immune-chemotherapy and Covid-19 vaccination. Despite treatment and negativization of CRMP-5 IgG, the patient's visual loss continued to progress.
RESPIRATORY MEDICINE AND RESEARCH
(2022)
Article
Oncology
Shah Zeb Khan, Luca Arecco, Cynthia Villarreal-Garza, Bhawna Sirohi, Noam F. Ponde, Baker Habeeb, Mariana Brandao, Hatem A. Azim, Arman Reza Chowdhury, Ivana Bozovic-Spasojevic, Iryna Kovalenko, Andrew Odhiambo, Fahmi Usman Seid, Alex Baleka Mutombo, Fernando Petracci, Radu Vidra, Sara C. Altuna, Mila Petrova, Hampig Raphael Kourie, Mehmet Akif Ozturk, Maria Grazia Razeti, Csongor Gyorgy Lengyel, Narmin Talibova, Elene Mariamidze, Karina Perez Sacardo, Narjust Duma, Bishal Gyawali, Dario Trapani, Marco Tagliamento, Matteo Lambertini
Summary: Limited evidence exists on knowledge, practice, and attitudes of physicians from low- and middle-income countries (LMICs) regarding fertility preservation and pregnancy after breast cancer. This study aimed to assess the knowledge, practice, and attitudes of physicians from LMICs on these issues through a questionnaire survey. The results showed suboptimal knowledge, practice, and attitudes, indicating the need for increased awareness and education to improve adherence to guidelines and promote oncofertility counseling for young women with breast cancer.
JCO GLOBAL ONCOLOGY
(2022)
