Article
Oncology
Anastasia A. Ionkina, Gabriela Balderrama-Gutierrez, Krystian J. Ibanez, Steve Huy D. Phan, Angelique N. Cortez, Ali Mortazavi, Jennifer A. Prescher
Summary: The study analyzed transcriptomes of metastatic breast cancer cells using the MMTV-PyMT mouse model to understand tumor heterogeneity and organ tropism. The results provided insights into metastatic progression and potential targets for breast cancer treatment, as well as the impact of tumor heterogeneity on metastasis.
BREAST CANCER RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Balazs Vari, Levente Dokus, Adina Borbely, Aniko Gaal, Diana Vari-Mezo, Ivan Randelovic, Anna Solyom-Tisza, Zoltan Varga, Norbert Szoboszlai, Gabor Mezo, Jozsef Tovari
Summary: Chemotherapy remains an important treatment for various types of tumors, but its poor prognosis is often due to metastases. PEGylated liposomes with CREKA targeting moiety have been widely used as therapeutic agents in highly metastatic experimental models. In this study, we designed different liposome formulations with varying amounts of targeting moieties attached to their DSPE-PEG molecules. We also developed a new tumor-homing pentapeptide (SREKA) and a novel conjugation strategy between SREKA and DSPE-PEGs. Our results showed that SREKA-liposomes exhibited similar characteristics and tumor-homing capabilities to CREKA-liposomes, but had higher production yield and better stability upon conjugation. SREKA-liposomes effectively inhibited primary tumor growth, reduced metastasis incidence, and improved the survival rate of tumor-bearing mice. Additionally, the amount of targeting moiety attached to DSPE-PEGs played a crucial role in the stability, toxicity, and targeting of the liposomes.
Article
Endocrinology & Metabolism
Mikaela M. Mallin, Kenneth J. Pienta, Sarah R. Amend
Summary: Metastatic cancer, especially bone metastases, is highly lethal. The determinants of bone-specific metastasis have remained unknown, although the sequential steps of metastasis have been studied extensively. This study proposes a new perspective on metastatic organotropism by applying ecological principles to cancer biology models. It suggests that bone-specific metastasis is the result of habitat selection by foraging cancer cells and that only a small subset of cells in a primary tumor possess this ability.
Article
Oncology
Xueyang Hu, Wenjun Chen, Fanfan Li, Pengfei Ren, Hongyang Wu, Congjun Zhang, Kangsheng Gu
Summary: This study investigated the altered expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and cell proliferation index (Ki-67) in primary and metastatic breast cancer lesions, and their correlation with clinicopathological factors and disease-free survival (DFS). The expression rates of ER, PR, HER2, and Ki-67 were inconsistent between primary and metastatic lesions. The size of the primary lesion was not correlated with altered receptor expression, but lymph node metastasis was. Patients with positive ER and PR expression in both primary and metastatic lesions had the longest DFS, while patients with negative expression had the shortest DFS. Changes in HER2 expression did not affect DFS. Patients with low Ki-67 expression had longer DFS than those with high expression. These findings suggest that the heterogeneity of ER, PR, HER2, and Ki-67 expression has important implications for treatment and prognosis.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Yang Li, Jun Cao, Jianfeng Wang, Weidong Wu, Liren Jiang, Xing Sun
Summary: This study found that IGF2BP3 plays an important role in the progression and distant metastasis of breast cancer and is closely associated with brain metastasis. Positive IGF2BP3 expression is related to decreased distant metastasis-free survival and the occurrence of brain metastasis in breast cancer patients. High IGF2BP3 expression is associated with the PD-1 checkpoint pathway, HER2-HER3 signaling, and epithelial-mesenchymal transition.
Article
Nanoscience & Nanotechnology
Z. Fereshteh, M. N. Dang, C. Wenck, E. S. Day, J. H. Slater
Summary: This study investigated the efficacy of inhibiting cancer cell binding to human lung microvascular endothelial cells (HMVEC-Ls) via antibody blocking of E-selectin using antibody-functionalized gold nanoshells (NS). The results demonstrated that E-selectin-targeted NS reduced the binding of MDA-MB-231 cancer cells to HMVEC-Ls by up to 41%, suggesting the potential of these conjugates in inhibiting cancer cell extravasation during metastasis.
ACS APPLIED NANO MATERIALS
(2023)
Article
Pharmacology & Pharmacy
Shasha Li, Ming Yang, Shuaishuai Teng, Kequan Lin, Yumei Wang, Yanmei Zhang, Wei Guo, Dong Wang
Summary: This study reveals the epigenetic regulation of genes in liver metastatic colorectal cancer cells and their heterogeneity. Liver metastatic CRC cells lose colon-specific chromatin accessible sites while gaining liver-specific ones. These cells exhibit characteristics similar to erythroid progenitors and hepatocytes, with increased expression of genes involved in oxidative phosphorylation and glycolysis. The moderate epigenetic activity of MHC and IFN response genes in these cells is associated with low response rates in checkpoint blockade immunotherapy.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Biology
Sixuan Li, Hongquan Zhang, Xiaofan Wei
Summary: DUBs play essential roles in regulating breast cancer development and progression by modulating expression, activity, and localization of key proteins. They have emerged as promising prognostic indicators and drug targets. Specific DUB inhibitors have been identified and hold potential for benefiting breast cancer patients in the future.
Review
Biochemistry & Molecular Biology
Rolando Vegliante, Ievgenia Pastushenko, Cedric Blanpain
Summary: Cancer cells within a tumor exist in different states that are associated with distinct functions, and identifying the gene regulatory networks underpinning each state is crucial for understanding tumor heterogeneity and vulnerabilities. These tumor states are spatially distributed and interact with specific stromal cells in the tumor microenvironment, and knowledge of tumor plasticity and transition states can lead to new strategies for improving cancer therapy.
Article
Chemistry, Physical
Guodong Cao, Wei Cao, Jiawei Zhang, Qing Chen, Junjie Chen, Qiang Chu, Qiang Sun, Maoming Xiong, Bo Chen, Xiang Li
Summary: In this study, we overcame the EPR defects via the MTM nanosystem, which can realize acute targeted delivery to the tumour site, lactate depletion, promoted reactive oxygen species (ROS) induction, and enhanced the effect of TPZ, demonstrating a potential synergistic combination of cancer therapy with better efficacy and biosafety.
Article
Multidisciplinary Sciences
John J. Kelly, Moe Saee-Marand, Nivin N. Nystrom, Melissa M. Evans, Yuanxin Chen, Francisco M. Martinez, Amanda M. Hamilton, John A. Ronald
Summary: The study utilized HITI CRISPR-Cas9 minicircle donors for precise targeted knock-in of reporter genes at safe harbor loci. Results showed higher knock-in efficiency and functional reporter gene activity with HITI vectors, enabling multi-modal longitudinal in vivo imaging of cells. This work demonstrates the first CRISPR-Cas9 HITI system for large DNA donor constructs at a safe harbor locus.
Letter
Oncology
Xingyi Pan, Jiaojiao Zhou, Qian Xiao, Kenji Fujiwara, Mengwen Zhang, Guanglan Mo, Wei Gong, Lei Zheng
Summary: The study revealed that tumor cells from pancreatic ductal adenocarcinoma (PDAC) with liver or lung-specific metastatic potentials induce different methylation and metabolic gene expression in cancer-associated fibroblasts (CAFs), affecting CAF phenotypes. CAFs from liver metastasis showed a more homogeneous phenotype, while CAFs from lung metastasis maintained heterogeneity.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Oncology
Jing Liang, Shouqi Wang, Guowei Zhang, Baoyu He, Qingli Bie, Bin Zhang
Summary: Studying the differences, heterogeneity, and interaction of tumor-specific endothelial cells (TECs) with the tumor microenvironment is crucial for developing specific anti-tumor angiogenesis therapies.
FRONTIERS IN ONCOLOGY
(2021)
Review
Immunology
Jordan W. Conway, Jorja Braden, James S. Wilmott, Richard A. Scolyer, Georgina V. Long, Ines Pires da Silva
Summary: Immunotherapy, especially immune checkpoint inhibitors, has been widely used in different cancer types. However, there are differences in response to immune checkpoint inhibitors at different metastatic sites. Understanding the tumor immune microenvironment at various organ sites can help explain the organ-specific patterns of response to immunotherapy. This review discusses the association between site of metastasis and response to immune checkpoint inhibitors and summarizes key clinical and pre-clinical findings on the immune microenvironment of specific metastatic sites. The ultimate goal is to develop personalized treatment approaches for patients with innate or acquired resistance to immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Chenfei Zhou, Changting Qiao, Jun Ji, Wenqi Xi, Jinling Jiang, Liting Guo, Junwei Wu, Feng Qi, Qu Cai, Steven W. M. Olde Damink, Jun Zhang
Summary: Organ-specific metastasis is a unique mode of metastasis in gastric cancer, and the role of exosomes in this process is not fully understood. This study aimed to investigate the biological functions of plasma exosome proteins and their correlation with organ-specific metastasis in gastric cancer. The results showed that ILK1 and CD14 were associated with organ-specific metastasis and played a role in regulating malignant behaviors in gastric cancer cells. These findings highlight the importance of exosome proteins in driving tumor metastasis and provide new insights into the mechanisms of organ-specific metastasis in gastric cancer.
Article
Oncology
Sarah Maguire, Eleni Perraki, Katarzyna Tomczyk, Michael E. Jones, Olivia Fletcher, Matthew Pugh, Timothy Winter, Kyle Thompson, Rosie Cooke, Alison Trainer, Paul James, Stig Bojesen, Henrik Flyger, Heli Nevanlinna, Johanna Mattson, Eitan Friedman, Yael Laitman, Domenico Palli, Giovanna Masala, Ines Zanna, Laura Ottini, Valentina Silvestri, Antoinette Hollestelle, Maartje J. Hooning, Srdjan Novakovic, Mateja Krajc, Manuela Gago-Dominguez, Jose Esteban Castelao, Hakan Olsson, Ingrid Hedenfalk, Emmanouil Saloustros, Vasilios Georgoulias, Douglas F. Easton, Paul Pharoah, Alison M. Dunning, D. Timothy Bishop, Susan L. Neuhausen, Linda Steele, Alan Ashworth, Montserrat Garcia Closas, Richard Houlston, Anthony Swerdlow, Nick Orr
Summary: This study identified three new susceptibility loci for male breast cancer, revealing a shared genetic basis with female breast cancer, and men in the top quintile of genetic risk had a fourfold increased risk of breast cancer compared to those in the bottom quintile.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Oncology
Sara Corvigno, Artur Mezheyeuski, Laura Martin De La Fuente, Sofia Westbom-Freme, Joseph W. Carlson, Josefin Fernebro, Elisabeth Avall-Lundqvist, Paivi Kannisto, Ingrid Hedenfalk, Susanne Malander, Charlotte Rolny, Hanna Dahlstrand, Arne Ostman
GYNECOLOGIC ONCOLOGY
(2020)
Article
Multidisciplinary Sciences
Pia Leandersson, Anna Akesson, Ingrid Hedenfalk, Susanne Malander, Christer Borgfeldt
Article
Oncology
Jenny-Maria Jonsson, Maria Baath, Ida Bjornheden, Irem Durmaz Sahin, Anna Masback, Ingrid Hedenfalk
Summary: Serous endometrial cancer (SEC) is an aggressive subtype with similarities to high-grade serous ovarian cancer (HGSOC), potentially benefiting from targeted treatments like PARP inhibitors. A study revealed that some SEC patients have homologous recombination repair deficiency, indicating a possible targeted therapy approach.
Article
Biochemistry & Molecular Biology
Maciej Ciesla, Phuong Cao Thi Ngoc, Eugenia Cordero, Alvaro Sejas Martinez, Mikkel Morsing, Sowndarya Muthukumar, Giulia Beneventi, Magdalena Madej, Roberto Munita, Terese Jonsson, Kristina Lovgren, Anna Ebbesson, Bjorn Nodin, Ingrid Hedenfalk, Karin Jirstrom, Johan Vallon-Christersson, Gabriella Honeth, Johan Staaf, Danny Incarnato, Kristian Pietras, Ana Bosch, Cristian Bellodi
Summary: The study uncovers the central role of the core splice factor SF3A3 in rewiring splicing during malignant transformation, particularly in the context of MYC hyperactivation. SF3A3 levels are modulated through translation in an elF3D-dependent manner, leading to metabolic reprogramming and stem-like properties that fuel MYC tumorigenic potential. Overall, these findings reveal a post-transcriptional interplay between splicing and translation that governs critical facets of MYC-driven oncogenesis.
Article
Genetics & Heredity
Maria Baath, Jenny-Maria Jonsson, Sofia Westbom Fremer, Laura Martin de la Fuente, Lena Tran, Susanne Malander, Paivi Kannisto, Anna Masback, Gabriella Honeth, Ingrid Hedenfalk
Summary: The study found that MET expression is associated with prognosis in high-grade serous ovarian cancer, especially in SOX2-negative tumors. In vitro experiments showed no synergistic effects of combined treatment with PARP and MET inhibitors in cell lines with BRCA1 or BRCA2 deficiencies.
Article
Oncology
A. Matikas, K. Wang, E. Lagoudaki, B. Acs, I Zerdes, J. Hartman, E. Azavedo, J. Bjohle, L. Carlsson, Z. Einbeigi, I Hedenfalk, M. Hellstrom, T. Lekberg, N. Loman, A. Saracco, A. von Wachenfeldt, S. Rotstein, M. Bergqvist, J. Bergh, T. Hatschek, T. Foukakis
Summary: The study highlights the potential value of TK1 activity as a prognostic marker in breast cancer patients. Changes in TK1 activity during chemotherapy were closely associated with patient survival outcomes, improving event-free survival and overall survival rates.
Article
Oncology
Jane Bayani, Coralie Poncet, Cheryl Crozier, Anouk Neven, Tammy Piper, Carrie Cunningham, Monika Sobol, Stefan Aebi, Kim Benstead, Oliver Bogler, Lissandra Dal Lago, Judith Fraser, Florentine Hilbers, Ingrid Hedenfalk, Larissa Korde, Barbro Linderholm, John Martens, Lavinia Middleton, Melissa Murray, Catherine Kelly, Cecilia Nilsson, Monika Nowaczyk, Stephanie Peeters, Aleksandra Peric, Peggy Porter, Carolien Schroder, Isabel T. Rubio, Kathryn J. Ruddy, Christi van Asperen, Danielle Van den Weyngaert, Carolien van Deurzen, Elise van Leeuwen-Stok, Joanna Vermeij, Eric Winer, Sharon H. Giordano, Fatima Cardoso, John M. S. Bartlett
Summary: The gene expression results of male breast cancer patients in the study demonstrate clinical utility in risk assessment and significant differences in prognosis based on different risk scores.
Article
Oncology
Johan Staaf, Jari Hakkinen, Cecilia Hegardt, Lao H. Saal, Siker Kimbung, Ingrid Hedenfalk, Tonje Lien, Therese Sorlie, Bjorn Naume, Hege Russnes, Rachel Marcone, Ayyakkannu Ayyanan, Cathrin Brisken, Rebecka R. Malterling, Bengt Asking, Helena Olofsson, Henrik Lindman, Par-Ola Bendahl, Anna Ehinger, Christer Larsson, Niklas Loman, Lisa Ryden, Martin Malmberg, Ake Borg, Johan Vallon-Christersson
Summary: Using RNA-sequencing, single-sample predictor (SSP) models were developed for clinical markers, subtypes, and risk of recurrence. The results show high consistency between the SSP models and Prosigna in terms of subtypes and risk categories, as well as for chemotherapy recommendations.
Article
Oncology
Hani Saghir, Srinivas Veerla, Martin Malmberg, Lisa Ryden, Anna Ehinger, Lao H. Saal, Johan Vallon-Christersson, Ake Borg, Cecilia Hegardt, Christer Larsson, Alaa Haidar, Ingrid Hedenfalk, Niklas Loman, Siker Kimbung
Summary: This study aimed to assess the reliability of using CNB for preoperative tumor characterization in early breast cancer. Results showed moderate to very good correlation between IHC and GEX assessment in paired CNB and surgical specimens, with some discrepancies observed in Ki67 and ER across different techniques, potentially impacting treatment decisions and patient outcomes.
Article
Biochemistry & Molecular Biology
Ahmad Nasimian, Mehreen Ahmed, Ingrid Hedenfalk, Julhash U. Kazi
Summary: In this study, a gene signature was defined through the analysis of cisplatin-perturbed gene expression and pathway enrichment, and a cisplatin sensitivity prediction model was developed using the TabNet algorithm. The TabNet model outperformed other machine learning models with an accuracy of over 80%. Furthermore, BCL2L1 was identified as an important gene contributing to cisplatin resistance, and its pharmacological inhibition was found to enhance cisplatin efficacy. This study developed a tool to predict cisplatin sensitivity and identified BCL2L1 as a significant gene in this context.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Oncology
Oscar Briem, Eva Kallberg, Siker Kimbung, Srinivas Veerla, Jenny Stenstrom, Thomas Hatschek, Catharina Hagerling, Ingrid Hedenfalk, Karin Leandersson
Summary: We found that CD169(+) macrophages in primary breast tumors are associated with tertiary lymphoid-like structures (TLLSs), T-reg and B-reg signatures, and a worse prognosis for the patient. However, CD169(+) macrophages and TLLSs in lymph node metastases are associated with a better prognosis. We propose that the negative prognostic value of CD169(+) macrophages and TLLSs in primary breast tumors is a unique consequence of an immunosuppressive tumor environment in advanced breast cancers.
Article
Oncology
Mads H. Haugen, Ole Christian Lingjaerde, Ingrid Hedenfalk, Oystein Garred, Elin Borgen, Niklas Loman, Thomas Hatschek, Anne-Lise Borresen-Dale, Bjorn Naume, Gordon B. Mills, Gunhild M. Maelandsmo, Olav Engebraaten
Summary: In breast cancer patients, a nine-protein signature score named vascular endothelial growth factor inhibition response predictor (ViRP) was identified to predict the effectiveness of treatment with bevacizumab combined with chemotherapy, based on the expression levels of selected proteins. This ViRP score was internally validated on mRNA data and also validated in an independent phase II clinical trial, showing promise in predicting treatment benefit in HER2-negative breast cancer patients.
JCO PRECISION ONCOLOGY
(2021)
Article
Oncology
Kamila Kaminska, Nina Akrap, Johan Staaf, Carla L. Alves, Anna Ehinger, Anna Ebbesson, Ingrid Hedenfalk, Lukas Beumers, Srinivas Veerla, Katja Harbst, Sidse Ehmsen, Signe Borgquist, Ake Borg, Alejandro Perez-Fidalgo, Henrik J. Ditzel, Ana Bosch, Gabriella Honeth
Summary: Resistance to endocrine treatment in metastatic breast cancer poses a major clinical challenge, with complex mechanisms contributing to the development of diverse resistance patterns, impacting levels of estrogen receptor independence and potential cross-resistance to CDK inhibitors.
BREAST CANCER RESEARCH
(2021)
Article
Oncology
Jenny Stenstrom, Ingrid Hedenfalk, Catharina Hagerling
Summary: This study investigated the immune landscape in metastatic breast cancer patients, revealing that T lymphocytes and Tregs were the most clinically important immune cell populations in primary tumors. Infiltration of T lymphocytes and Tregs correlated with proliferation and estrogen receptor negativity, and T lymphocyte infiltration was an independent prognostic factor for recurrence-free survival while Treg infiltration was an independent prognostic factor for breast cancer-specific survival.
BREAST CANCER RESEARCH
(2021)