Article
Oncology
Elie Rassy, Layal Rached, Barbara Pistilli
Summary: The identification and development of HER-targeting antibody-drug conjugates (ADCs) have greatly improved the survival outcomes for breast cancer patients, particularly in the second and third-line settings. Despite promising activity in preclinical and clinical studies, there are still challenges to overcome, such as understanding resistance mechanisms and optimizing treatment for specific patient subgroups. Future research and clinical trials will help further enhance the efficacy of HER-targeting ADCs in breast cancer treatment.
Article
Engineering, Multidisciplinary
Ernesto A. B. F. Lima, Reid A. F. Wyde, Anna G. Sorace, Thomas E. Yankeelov
Summary: This study optimizes the treatment regimen for HER2+ breast cancer using mathematical modeling and optimal control theory. By analyzing experimental data and calibrating models, the optimal treatment protocol is determined, highlighting the benefits of pre-treatment with trastuzumab and doxorubicin for tumor control. These findings emphasize the importance of mathematical modeling and optimal control theory in optimizing treatment regimens.
COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Agnieszka Drzal, Anthony Delalande, Gabriela Dziurman, Chantal Pichon, Jan Swakon, Martyna Elas
Summary: The inadequate oxygenation in tumors is associated with increased invasiveness of cancer cells and reduced sensitivity to anticancer therapies. Attempts to increase tumor oxygenation have been largely ineffective. The use of phospholipid-coated oxygen microbubbles (OMB) can increase tumor oxygenation, but it also affects tumor vasculature and promotes cancer cell spread.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Oncology
Mythili Shastry, Saya Jacob, Hope S. Rugo, Erika Hamilton
Summary: Antibody drug conjugates (ADCs) combine the cytotoxicity of chemotherapy and the targeted therapy of antibodies into a single molecule. TROP-2, a transmembrane glycoprotein, is expressed in multiple tumor types, especially in HER2-negative breast tumors, and is associated with worse survival. Sacituzumab govitecan (SG) is a first-in-class TROP-2-directed ADC that has shown significant improvement in progression-free survival and overall survival in pretreated metastatic triple-negative breast cancer. Datopotamab deruxtecan (Dato-DXd) is another TROP-2 ADC that has demonstrated preliminary efficacy in unselected metastatic TNBC. Both SG and Dato-DXd have the potential to deliver enhanced efficacy with reduced toxicity in breast cancer.
Review
Biochemistry & Molecular Biology
Ganji Seeta Rama Raju, Eluri Pavitra, Sai Samyuktha Bandaru, Ganji Lakshmi Varaprasad, Ganji Purnachandra Nagaraju, Rama Rao Malla, Yun Suk Huh, Young-Kyu Han
Summary: HOTAIR is an oncogenic non-coding RNA that is strongly associated with tumor grade and prognosis in various carcinomas, including breast cancer (BC). It regulates target genes through sponging and epigenetic mechanisms and controls oncogenic cellular and signaling mechanisms, such as metastasis and drug resistance. In BC cells, HOTAIR expression is regulated by transcriptional and epigenetic mechanisms. This review discusses the regulatory mechanisms of HOTAIR during cancer development and explores its role in BC development, metastasis, and drug resistance. The review also highlights the potential therapeutic applications of HOTAIR in BC management, treatment, and prognosis.
Article
Pharmacology & Pharmacy
Ophelia Yin, Hiroji Iwata, Chia-Chi Lin, Kenji Tamura, Junichiro Watanabe, Russ Wada, Helen Kastrissios, Malaz AbuTarif, Tushar Garimella, Caleb Lee, Lin Zhang, Javad Shahidi, Frank LaCreta
Summary: Trastuzumab deruxtecan (T-DXd) has been approved for HER2-positive metastatic breast cancer and gastric cancer, with the 5.4 mg/kg every-3-weeks dosage justified based on exposure-efficacy analysis. Intact T-DXd area under the concentration-time curve was significantly associated with objective response rate, while no significant exposure-response relationships were observed for duration of response or progression-free survival. Higher exposure to T-DXd or released drug was correlated with increased adverse events, suggesting a dose-response relationship with higher ORR and toxicity at 6.4 mg/kg compared to 5.4 mg/kg.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Fanny Leenhardt, Frederic Fiteni, Ludovic Gauthier, Marie Alexandre, Severine Guiu, Nelly Firmin, Stephane Pouderoux, Marie Viala, Gerald Lossaint, Chloe Gautier, Caroline Mollevi, Matthieu Gracia, Celine Gongora, Litaty Mbatchi, Alexandre Evrard, William Jacot
Summary: This study confirms the importance of therapeutic drug monitoring (TDM) in managing the safe use of Palbociclib, particularly in relation to hematological toxicity. The study also highlights the significance of characterizing co-treatments to limit the risk of drug-drug interactions (DDI) with oral-targeted therapies.
Article
Biology
Takashi Ogino, Naoya Matsunaga, Takahiro Tanaka, Tomohito Tanihara, Hideki Terajima, Hikari Yoshitane, Yoshitaka Fukada, Akito Tsuruta, Satoru Koyanagi, Shigehiro Ohdo
Summary: The disruption of circadian clock machinery in cancer cells is associated with tumor malignancy. High ALDH activity in breast cancer stem-like cells is negatively regulated by the major circadian component CLOCK. The inhibition of CLOCK expression by miR-182 affects the stemness properties of breast cancer cells, suggesting a novel strategy for breast cancer treatment.
Article
Oncology
Vic Zamloot, Nancy Danielle Ebelt, Catherine Soo, Shweta Jinka, Edwin R. Manuel
Summary: Breast cancer often contains excessive stromal matrix components, such as hyaluronic acid (HA), which plays important roles in tumor progression and spread. This study shows that an attenuated Salmonella typhimurium secreting a bacterial hyaluronidase (YS-HAse) can degrade HA within murine breast tumors, resulting in enhanced tumor permeability and growth control. YS-HAse represents a promising new therapeutic approach that could be used alongside current treatments to improve their delivery and effectiveness.
Article
Oncology
Qian Wu, Ming-Shuai Sun, Yin-Hua Liu, Jing-Ming Ye, Ling Xu
Summary: This study aims to identify risk factors and establish a competing risk model for predicting brain metastases in patients with metastatic breast cancer. The model showed good discrimination, calibration, and clinical utility, and was more accurate than traditional models in predicting the risk of brain metastases.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Engineering, Biomedical
Naledi Shologu, Mehmet Gurdal, Eva Szegezdi, Una FitzGerald, Dimitrios I. Zeugolis
Summary: This study evaluated the potential of macromolecular crowding in improving cell-derived matrices for in vitro tumor models. NP40 was the most effective decellularisation protocol in removing cellular matter while preserving the deposited matrix. Macromolecular crowding derived matrices produced by mammary fibroblasts showed increased adhesion molecules, metalloproteinases, and proinflammatory cytokines, as well as enhanced resistance to doxorubicin and reduced cell death caused by reactive oxygen species.
Article
Immunology
Zaid Taha, Mathieu J. F. Crupi, Nouf Alluqmani, Faiha Fareez, Kristy Ng, Judy Sobh, Emily Lee, Andrew Chen, Max Thomson, Marcus M. Spinelli, Carolina S. Ilkow, John C. Bell, Rozanne Arulanandam, Jean-Simon Diallo
Summary: Researchers successfully established a syngeneic mouse model of huHER2+ breast cancer, which can be used to evaluate immunotherapies targeting human HER2. By using a truncated form of huHER2 called HER2T, the researchers treated breast cancer mice and found significant anti-tumor effects and immune memory. The results demonstrated the utility of this syngeneic mouse model for evaluating the efficacy of HER2-targeted therapies in an immunocompetent in vivo setting.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Engineering, Biomedical
Chun Liu, Miao Li, Zhao-Xia Dong, Dong Jiang, Xiaojing Li, Shuibin Lin, Demeng Chen, Xuenong Zou, Xing-Ding Zhang, Gary D. Luker
Summary: The study showed that breast cancer cells behave differently in environments with different stiffness: cells tend to proliferate in soft environments and migrate in stiff environments. Breast cancer cells switch metabolic pathways and gene expression in response to varying environmental stiffness.
ACTA BIOMATERIALIA
(2021)
Review
Oncology
Nuhad K. Ibrahim
Summary: The epothilone drug class, including ixabepilone, has shown efficacy and safety in the treatment of metastatic breast cancer, demonstrating improved progression-free survival and overall response rates in patients who have progressed during chemotherapy. Additionally, ixabepilone's clinical benefit in special populations has been characterized, with evidence supporting its use in specific patient groups such as those with triple-negative breast cancer. Dose reductions do not appear to impact the efficacy of ixabepilone, making it a valuable option for individualized treatment plans in patients with unmet needs.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Shou-Ching Tang, Carter L. Capra, Germame H. Ajebo, Judith Meza-Junco, Simon Mairs, Barbara S. Craft, Xiaofu Zhu, Nita Maihle, William B. Hillegass
Summary: This study indicates that the systemic toxicities of T-DM1 are significantly correlated with its clinical efficacy, with a higher toxicity sum score associated with longer progression-free survival.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Oncology
Rongrong Wu, Ankit Patel, Yoshihisa Tokumaru, Mariko Asaoka, Masanori Oshi, Li Yan, Takashi Ishikawa, Kazuaki Takabe
Summary: RAD51 gene expression is associated with aggressive cancer biology, cancer cell proliferation, and poor survival in breast cancer.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Article
Oncology
Masanori Oshi, Shipra Gandhi, Li Yan, Yoshihisa Tokumaru, Rongrong Wu, Akimitsu Yamada, Ryusei Matsuyama, Itaru Endo, Kazuaki Takabe
Summary: The study aimed to investigate the clinical relevance of reactive oxygen species (ROS) in the breast cancer tumor microenvironment. The results showed that high ROS levels were significantly associated with cell proliferation-related genes, pro-cancer genes, immune-related genes, infiltrated immune cells, and increased cytolytic activity. High ROS was also associated with intratumor heterogeneity, mutation rates, immune response, and worse survival outcomes.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Review
Oncology
Ravi Kumar Gupta, Arya Mariam Roy, Ashish Gupta, Kazuaki Takabe, Ajay Dhakal, Mateusz Opyrchal, Pawel Kalinski, Shipra Gandhi
Summary: This article summarizes emerging opportunities to use less toxic therapies in early-stage triple-negative breast cancer (TNBC), providing a personalized approach for patients. It reviews completed and ongoing clinical trials and provides guidance on stratifying patients to maximize benefits without unnecessary toxicities.
Article
Oncology
Rongrong Wu, Shipra Gandhi, Yoshihisa Tokumaru, Mariko Asaoka, Masanori Oshi, Li Yan, Takashi Ishikawa, Kazuaki Takabe
Summary: This study found that PDGFB gene expression is associated with angiogenesis and lymphangiogenesis in breast cancer patients, but not with cellular proliferation or metastasis.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Article
Biotechnology & Applied Microbiology
Nitai C. Hait, Aparna Maiti, Rongrong Wu, Valerie L. Andersen, Chang-Chieh Hsu, Yun Wu, Digantkumar G. Chapla, Kazuaki Takabe, Michael E. Rusiniak, Wiam Bshara, Jianmin Zhang, Kelley W. Moremen, Joseph T. Y. Lau
Summary: Our study found that extracellular ST6GAL1 can compensate for insufficient cellular ST6GAL1, promoting cancer cell proliferation and invasiveness. Moreover, we identified novel cofactors in the exosome-like particles that amplify the action of extrinsic ST6GAL1. Overall, this study reveals the importance of ST6GAL1 in tumor pathobiology.
CANCER GENE THERAPY
(2022)
Article
Oncology
Rongrong Wu, Arya Mariam Roy, Yoshihisa Tokumaru, Shipra Gandhi, Mariko Asaoka, Masanori Oshi, Li Yan, Takashi Ishikawa, Kazuaki Takabe
Summary: Tumor dormancy is an important mechanism for late breast cancer recurrence. This study investigates the clinical relevance of NR2F1 expression, a known biomarker for dormancy. The results show that high NR2F1 expression in breast cancer is associated with enriched metastasis and stem cell-related pathways, as well as suppressed cell proliferation. Furthermore, NR2F1 is predominantly expressed in cancer-associated fibroblasts, rather than in cancer cells.
Article
Biochemistry & Molecular Biology
Eriko Katsuta, Kazuaki Takabe, Marija Vujcic, Philip A. Gottlieb, Tao Dai, Arnaldo Mercado-Perez, Arthur Beyder, Qingfei Wang, Mateusz Opyrchal
Summary: High expression of PIEZO2 in breast cancer, particularly in triple-negative breast cancer (TNBC), is associated with worse clinical outcomes. Activation of PIEZO2 leads to increased cell motility and invasive phenotypes, as well as the upregulation of epithelial-mesenchymal transition (EMT)-related genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Fernando A. Angarita, Robert Brumer, Matthew Castelo, Nestor F. Esnaola, Stephen B. Edge, Kazuaki Takabe
Summary: De-escalation of breast cancer treatment can reduce morbidity and improve patients' quality of life. It is considered safe if the cancer outcomes are not affected compared to more aggressive treatments. This review provides an overview of de-escalation in the treatment of ductal carcinoma in situ (DCIS), local treatment of breast cancer, and surgery after neoadjuvant systemic therapy. Advancements in understanding the natural history and biology of breast cancer, imaging techniques, and adjuvant treatments have allowed for the reduction of treatment intensity. Identifying appropriate areas for de-escalation is crucial to minimize side effects while maintaining cancer outcomes. Less aggressive treatment modalities, or even no treatment, have been reconsidered if they achieve similar oncologic results as standard therapies. Careful consideration is needed to identify which patients benefit from de-escalation, as standard therapies still offer adequate cancer outcomes. This review highlights the importance of investigating de-escalation in breast cancer treatment, with future efforts aiming to clarify the role of different treatment modalities.
Editorial Material
Oncology
Joy Sarkar, Hiroaki Aoki, Rongrong Wu, Masayo Aoki, Phillip Hylemon, Huiping Zhou, Kazuaki Takabe
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Joy Sarkar, Hiroaki Aoki, Rongrong Wu, Masayo Aoki, Phillip Hylemon, Huiping Zhou, Kazuaki Takabe
Summary: This study found that conjugated bile acids (CBAs) accumulated in cholestasis accelerate the growth of pancreatic cancer (PC) through S1PR2, indicating S1PR2 as a potential therapeutic target for metastatic pancreatic cancer.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Review
Cell Biology
Irene Yu, Anthony Dakwar, Kazuaki Takabe
Summary: Immunotherapy has shown significant progress in the treatment of colorectal cancer (CRC) in the past decade. Immune checkpoint inhibitors have been particularly effective in improving patient outcomes in a specific subset of CRC. The efficacy and timing of immunotherapy for other subsets of CRC have gained attention, and this review discusses the latest advances and future directions for three main classes of immunotherapy for CRC: immune checkpoint inhibitors, adoptive cell transfer therapy, and tumor vaccines.
Article
Biochemistry & Molecular Biology
Matthew G. K. Benesch, Rongrong Wu, Xiaoyun Tang, David N. Brindley, Takashi Ishikawa, Kazuaki Takabe
Summary: Lysophosphatidic acid receptors (LPARs) play a role in promoting tumorigenesis and therapy resistance in various cancer subtypes. Our study found that increased expression of LPAR1, LPAR4, and LPAR6 correlated with a less aggressive phenotype, while high expression of LPAR2 was associated with increased tumor grade, mutational burden, and decreased survival. Different LPARs were also expressed in different cell types, suggesting potential compensatory signaling in LPAR inhibitor therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Surgery
Kohei Chida, Masanori Oshi, Arya Mariam Roy, Takafumi Yachi, Masaki Nara, Kyogo Yamada, Osamu Matsuura, Tadashi Hashizume, Itaru Endo, Kazuaki Takabe
Summary: This study found that the E2F target score, reflecting the activity of E2F target genes, is associated with the aggressiveness and prognosis of hepatocellular carcinoma. High E2F target score is associated with tumor grade, size, staging, proliferation score, MKI67 expression, as well as reduced abundance of hepatocytes and stromal cells. It is also associated with higher intratumoral genomic heterogeneity, homologous recombination deficiency, and progression of hepatocellular carcinoma.
Article
Oncology
Matthew G. K. Benesch, Rongrong Wu, Xiaoyun Tang, David N. Brindley, Takashi Ishikawa, Kazuaki Takabe
Summary: The lipid phosphate phosphatases (LPPs) are enzymes that regulate signaling in cells. Imbalance of LPP expression levels, with decreased LPP1/3 and increased LPP2, is associated with worse tumor biology, immune system evasion, and decreased survival in breast cancers. Most tumor LPP1/3 is produced by the stroma and LPP2 by cancer cells. Restoring the balance in LPP expression levels, particularly through LPP2 inhibition, could provide adjunct therapies for breast cancer patients.
Article
Oncology
Joy Sarkar, Hiroaki Aoki, Rongrong Wu, Masayo Aoki, Phillip Hylemon, Huiping Zhou, Kazuaki Takabe
Summary: This study found that conjugated bile acids (CBAs) accelerate the growth of S1PR2 predominant pancreatic cancer, suggesting that S1PR2 may be a potential therapeutic target for metastatic pancreatic cancer.
ANNALS OF SURGICAL ONCOLOGY
(2023)
