Article
Oncology
Yifan Xie, Siyu Wu, Ying Zhang, Jianwei Li, Miao Mo, Zhimin Shao, Guangyu Liu
Summary: The study aimed to investigate the optimal number of cycles of neoadjuvant TCH therapy for HER2-positive breast cancer patients and found no significant difference in terms of pathological complete response rate and four-year event-free survival rate between four and six cycles. Negative hormone receptor status and weekly paclitaxel were independent factors for predicting pCR. Four cycles of taxane/carboplatin-based neoadjuvant anti-HER2 therapy may be applied as an optimal treatment duration for screening high-risk HER2-positive breast cancer patients for escalation treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Worapol Ngamcherdtrakul, Daniel S. Bejan, William Cruz-Munoz, Moataz Reda, Husam Y. Zaidan, Natnaree Siriwon, Suphalak Marshall, Ruijie Wang, Molly A. Nelson, Justin P. C. Rehwaldt, Joe W. Gray, Kullervo Hynynen, Wassana Yantasee
Summary: The first-line treatment of advanced and metastatic human epidermal growth factor receptor type 2 (HER2+) breast cancer requires a combination of two antibodies and a taxane. However, this treatment is expensive, time-consuming, and has limited efficacy. To overcome these limitations, a single therapeutic based on nanoparticles has been developed, which can co-deliver drugs and siRNA to specifically target HER2-positive breast cancer cells.
Review
Biochemistry & Molecular Biology
Hailong Chen, Mengwen Zhang, Yongchuan Deng
Summary: Breast cancer is a common and deadly disease among women. Chemotherapy, particularly taxanes, has greatly improved the prognosis of breast cancer patients. However, taxane resistance caused by various factors remains a challenge. Long noncoding RNAs (lncRNAs) have been found to play a significant role in taxane resistance. This review systematically summarizes the mechanisms of taxane resistance in breast cancer and the functions of lncRNAs in this resistance. The findings suggest that lncRNAs may serve as therapeutic targets to prevent or reverse taxane resistance in breast cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Changfa Shu, Xi Zheng, Alafate Wuhafu, Danielle Cicka, Sean Doyle, Qiankun Niu, Dacheng Fan, Kun Qian, Andrey A. Ivanov, Yuhong Du, Xiulei Mo, Haian Fu
Summary: This study reveals an association between TP53 status and taxane sensitivity in ovarian cancer cells. TP53 inactivation is associated with taxane resistance, and TP53-dependent gene expression patterns may serve as predictive biomarkers of taxane resistance. Additionally, the TP53-dependent hyperactivation of the WNT/β-catenin pathway suggests a potential vulnerability to exploit in developing combination therapeutic strategies.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Pharmacology & Pharmacy
Min Sun, Xiaoxiao Liu, Lingyun Xia, Yuying Chen, Li Kuang, Xinsheng Gu, Tian Li
Summary: A nine-lncRNA prognostic risk score model was developed to predict distant relapse-free survival of patients with HER2-negative breast cancer following taxane and anthracycline-based neoadjuvant chemotherapy. This model showed robust predictive power compared to other prognostic markers and could differentiate survival probability between different expression levels of the lncRNAs.
BIOCHEMICAL PHARMACOLOGY
(2021)
Editorial Material
Medicine, General & Internal
Ron Bose, Cynthia X. Ma
Summary: A recent study suggests that HER2-mutated breast cancer may develop resistance to drugs that inhibit the tyrosine kinase domain of HER2 through developing mutations in HER3, which enhance the dimerization between HER2 and HER3. The HER3 mutations augment signaling. This study supports a specific approach to overcoming mutant-HER3-mediated resistance.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Oncology
Hao Liu, Hui Lyu, Guanmin Jiang, Danyang Chen, Sanbao Ruan, Shuang Liu, Lukun Zhou, Minqiang Yang, Shanshan Zeng, Zhimin He, Hongsheng Wang, Hongsheng Li, Guopei Zheng, Bolin Liu
Summary: Resistance to HER2-targeted therapy in breast cancer is associated with upregulation of ALKBH5, which promotes m6A demethylation of GLUT4 mRNA, leading to increased glycolysis and resistance to therapy. ALKBH5 and GLUT4 overexpression are associated with poor prognosis. Inhibiting GLUT4 may restore response to HER2-targeted therapy.
Review
Oncology
Santiago Duro-Sanchez, Macarena Roman Alonso, Joaquin Arribas
Summary: A variety of treatments are available for HER2-positive breast cancer, but resistance to these therapies is common and associated with poor prognosis. Immunotherapeutic approaches are being explored to eradicate tumor cells and prevent relapse and progression. This review discusses the different immunotherapeutic strategies being tested and their potential benefits for HER2-positive breast cancer.
Review
Medicine, General & Internal
Aashna Patel, Roshni Kalachand, Steven Busschots, Ben Doherty, Evangelos Kapros, Denise Lawlor, Neville Hall, Britta K. Stordal
Summary: The study evaluated the efficacy and toxicity of different taxane monotherapy regimens for women with recurrent epithelial ovarian, tubal, or primary peritoneal cancer. The weekly paclitaxel regimen may reduce the risk of neutropenia and alopecia, while its impact on neurotoxicity is uncertain. In the three-weekly paclitaxel regimen, a dose of 175 mg/m(2) probably reduces the risk of neurotoxicity.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2022)
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.
Article
Multidisciplinary Sciences
Nindo B. Punturi, Sinem Seker, Vaishnavi Devarakonda, Aloran Mazumder, Rashi Kalra, Ching Hui Chen, Shunqiang Li, Tina Primeau, Matthew J. Ellis, Shyam M. Kavuri, Svasti Haricharan
Summary: Resistance to endocrine treatment in ER+ breast cancer patients is linked to activation of HER2 due to loss of mismatch repair, and inhibiting HER2 restores sensitivity to treatment. Loss of MutL and upregulation of HER2 are associated with sensitivity to HER inhibitors in ER+/HER2(-) patients.
NATURE COMMUNICATIONS
(2021)
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
Erika Hamilton, Mythili Shastry, S. Michelle Shiller, Rongqin Ren
Summary: The heterogeneity of HER2 expression in breast cancer is being recognized as an important factor that impacts treatment outcomes, with the development of novel therapies to target tumors with non-uniform HER2 expression.
CANCER TREATMENT REVIEWS
(2021)
Article
Multidisciplinary Sciences
Muhammad Raisul Abedin, Kaitlyne Powers, Rachel Aiardo, Dibbya Barua, Sutapa Barua
Summary: Novel antibody-drug nanoparticles were designed for targeted and efficient anti-cancer therapy through selective targeting and cancer cell death via apoptosis and mitotic cell cycle arrest, showing higher therapeutic efficiency compared to individual drug treatments.
SCIENTIFIC REPORTS
(2021)
Article
Environmental Sciences
Tzu-Chao Chuang, Guan-Shiun Fang, Shih-Chung Hsu, Yi-Jen Lee, Wei-Syun Shao, Vinchi Wang, Shou-Lun Lee, Ming-Ching Kao, Chien-Chih Ou
Summary: It has been found that baicalein can inhibit the proliferation and transformation potential of ovarian cancer cells overexpressing HER2. Baicalein suppresses HER2 gene expression at the transcriptional level, affecting the PI3K/Akt signaling pathway downstream of HER2 and inhibiting the expression or activity of downstream targets such as VEGF, cyclin D1, and MMP2. In addition, oral administration of baicalein significantly inhibits the growth of HER2-overexpressing ovarian SKOV-3 cancer xenografts in mice.
ENVIRONMENTAL TOXICOLOGY
(2023)
Review
Genetics & Heredity
Kateryna Kratzer, Landon J. Getz, Thibaut Peterlini, Jean-Yves Masson, Graham Dellaire
Summary: Gene therapy for genetic diseases has gained increased attention, but faces technical challenges and ethical barriers. Current research is primarily focused on improving gene therapy and gene editing techniques, with less emphasis on the timing and rationale for using such technology.
Article
Obstetrics & Gynecology
Cecile Le Page, Noorah Almadani, Gulisa Turashvili, Guillaume Bataillon, Lise Portelance, Diane Provencher, Anne-Marie Mes-Masson, Blake Gilks, Lien Hoang, Kurosh Rahimi
Summary: Immunohistochemical evaluation of SATB2 expression in various types of uterine sarcomas suggests it may serve as a marker for distinguishing between endometrial stromal nodules and ESS with potential prognostic value, particularly in low-grade ESS patients.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Livia E. Clarke, Allyson Cook, Sabateeshan Mathavarajah, Amit Bera, Jayme Salsman, Elias Habib, Carter Van Iderstine, Moamen Bydoun, Stephen M. Lewis, Graham Dellaire
Summary: PRP4K is an essential gene that when reduced is associated with aggressive breast and ovarian cancer phenotypes, leading to increased cell migration and invasion. These effects suggest that PRP4K functions as a haploinsufficient tumor suppressor.
Article
Oncology
Meshach Asare-Werehene, Hideaki Tsuyoshi, Huilin Zhang, Reza Salehi, Chia-Yu Chang, Euridice Carmona, Clifford L. Librach, Anne-Marie Mes-Masson, Chia-Ching Chang, Dylan Burger, Yoshio Yoshida, Benjamin K. Tsang
Summary: Ovarian cancer is a deadly disease primarily due to late diagnosis, recurrence, and chemoresistance. This study demonstrates that the over-expression of plasma gelsolin (pGSN) downregulates the anti-tumor functions of M1 macrophages, leading to chemoresistance and poor patient survival. Understanding the immunological role of pGSN in the tumor microenvironment can help improve the effectiveness of immunotherapy for ovarian cancer patients.
Review
Genetics & Heredity
Elias B. Habib, Sabateeshan Mathavarajah, Graham Dellaire
Summary: Pre-mRNA processing factor 4 kinase (PRP4K) is a conserved kinase that plays important roles in spliceosomal assembly. However, recent studies have revealed that PRP4K is also involved in various cellular pathways, including transcription regulation, spindle assembly checkpoint, and tumor suppression, contributing to tumorigenesis and chemotherapy response.
FRONTIERS IN GENETICS
(2022)
Article
Oncology
Charles Dariane, Sylvie Clairefond, Benjamin Peant, Laudine Communal, Zhe Thian, Veronique Ouellet, Dominique Trudel, Nazim Benzerdjeb, Feryel Azzi, Arnaud Mejean, Marc-Olivier Timsit, Manon Baures, Jacques-Emmanuel Guidotti, Vincent Goffin, Pierre I. Karakiewicz, Anne-Marie Mes-Masson, Fred Saad
Summary: Keratin-7 overexpression is associated with poor prognosis in several cancers, and its high expression in benign glands surrounding localized prostate tumors is correlated with shorter bone metastasis-free survival and increased risk of cancer-specific mortality. In prostate cancer patients, high Keratin-7 expression is significantly associated with hypertrophic basal cell phenotype.
Article
Oncology
Maxime Cahuzac, Benjamin Peant, Anne-Marie Mes-Masson, Fred Saad
Summary: This study established new models of resistance in prostate cancer cells and identified potential targets, such as DNA repair, autophagy, and ROCK2, to reverse acquired olaparib-resistance.
Article
Oncology
Karen Geoffroy, Patrick Laplante, Sylvie Clairefond, Feryel Azzi, Dominique Trudel, Jean-Baptiste Lattouf, John Stagg, Fred Saad, Anne-Marie Mes-Masson, Marie-Claude Bourgeois-Daigneault, Jean-Francois Cailhier
Summary: This study analyzed the distribution and prognostic impact of MFG-E8 protein expression in patients with prostate and renal cancers. It found that low levels of MFG-E8 were associated with worse clinical outcomes and that higher numbers of CD206(+) cells were found in the peripheral regions of renal clear cell carcinoma with lower MFG-E8 levels. The study suggests that MFG-E8 expression could potentially be used as a prognostic marker in prostate and renal cancers.
Article
Cell Biology
Xiaotong Jia, Anastasia Knyazeva, Yu Zhang, Sergio Castro-Gonzalez, Shuhei Nakamura, Lars-Anders Carlson, Tamotsu Yoshimori, Dale P. Corkery, Yao-Wen Wu
Summary: Jia et al. have identified cholesterol as the primary lipid responsible for the interaction between Vibrio cholerae toxin MakA and host membranes. They have also characterized a sophisticated mechanism of recurrent membrane damage regulated by pH-dependent pore formation, leading to V-ATPase-dependent unconventional LC3 lipidation on damaged endolysosomal membranes.
JOURNAL OF CELL BIOLOGY
(2022)
Editorial Material
Cell Biology
Dale P. Corkery, Yao-Wen Wu
Summary: Extracellular pathogens utilize secreted virulence factors to regulate host cell function. Recently, the molecular mechanism behind host macroautophagy/autophagy regulation by the Vibrio cholerae toxin MakA has been characterized. Cholesterol binding at the plasma membrane induces MakA endocytosis and pH-dependent pore assembly. Membrane perforation of late endosomal membranes induces cellular membrane repair pathways and V-ATPase-dependent unconventional LC3 lipidation on damaged membranes.
Article
Biochemistry & Molecular Biology
Tharindu L. Suraweera, J. P. Jose Merlin, Graham Dellaire, Zhaolin Xu, H. P. Vasantha Rupasinghe
Summary: Cancer is a leading cause of death globally, but current treatments like chemotherapy and radiation therapy have significant side effects. Therefore, the prevention of cancer through dietary modifications has gained interest. This study examined the potential of selected flavonoids in reducing reactive oxygen species (ROS) and DNA damage induced by carcinogens through the activation of the Nrf2/ARE pathway. The results showed that genistein and PCB2 could effectively reduce ROS and DNA damage, and further research is needed to understand the role of dietary flavonoids in regulating the Nrf2/ARE pathway in carcinogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sabateeshan Mathavarajah, Graham Dellaire
Summary: The cGAS-STING pathway integrates DNA damage and cellular stress with type I interferon signaling, and the dysregulation of this pathway is associated with various diseases. L1 retroelements play a crucial role in the induction of cGAS-STING and interferon signaling. TREX1 is an important suppressor of cGAS-STING and L1 activity, and its loss leads to the accumulation of L1 retroelements.
BIOCHEMISTRY AND CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dale Corkery, Andrei Ursu, Belen Lucas, Michael Grigalunas, Simon Kriegler, Rosario Oliva, Robert Dec, Sandra Koska, Axel Pahl, Sonja Sievers, Slava Ziegler, Roland Winter, Yao-Wen Wu, Herbert Waldmann
Summary: Lipidation of LC3 is often used to study autophagy, but it can be triggered by other stimuli as well. Inducin, a pseudo-natural product, increases LC3 lipidation independently of autophagy and impairs lysosomal function, leading to cell death.
Article
Biochemistry & Molecular Biology
Dale P. Corkery, Sergio Castro-Gonzalez, Anastasia Knyazeva, Laura K. Herzog, Yao-Wen Wu
Summary: This study reveals a novel role for TECPR1 in lysosomal membrane repair. TECPR1 is recruited to damaged membranes and forms a complex to regulate LC3 modification. The impairment of LC3 modification due to the double knockout of ATG16L1 and TECPR1 hinders lysosomal recovery.
Article
Evolutionary Biology
Sabateeshan Mathavarajah, Andrew W. Thompson, Matthew R. Stoyek, T. Alexander Quinn, Stephane Roy, Ingo Braasch, Graham Dellaire
Summary: This study reveals that aquatic vertebrates undergo transcriptional rewiring of innate immune signaling pathways during limb and fin regeneration to promote immune cell recruitment. The study also shows that cGAS-STING pathway and various suppressors of cytosolic DNA play important roles in the regeneration process. The findings provide insights into the molecular mechanisms behind tissue regeneration in aquatic animals.
JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION
(2023)