Article
Multidisciplinary Sciences
Jacopo Millul, Gabriele Bassi, Jacqueline Mock, Abdullah Elsayed, Christian Pellegrino, Aureliano Zana, Sheila Dakhel Plaza, Lisa Nadal, Andreas Gloger, Eleonore Schmidt, Ilaria Biancofiore, Etienne J. Donckele, Florent Samain, Dario Neri, Samuele Cazzamalli
Summary: OncoFAP is a high-affinity ligand of FAP with pan-tumoral potential, showing strong tumor-targeting performance in nude mouse models. It can also serve as a modular component for nonradioactive therapeutic products, highlighting its potential applications in tumor treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Sara Cherradi, Veronique Garambois, Johanna Marines, Augusto Faria Andrade, Alexandra Fauvre, Olivia Morand, Manon Fargal, Ferial Mancouri, Adeline Ayrolles-Torro, Nadia Vezzo-Vie, Marta Jarlier, Gerald Loussaint, Steve Huvelle, Nicolas Joubert, Thibault Mazard, Celine Gongora, Philippe Pourquier, Florence Boissiere-Michot, Maguy Del Rio
Summary: The expression of the tight junctional protein claudin 1 (CLDN1) in liver metastases of colorectal cancer (CRC) patients after chemotherapy was found to be significantly correlated with the histologic response to chemotherapy. Further experiments showed that conventional chemotherapies used in CRC treatment could induce CLDN1 expression, which was associated with resistance to apoptosis. Targeting chemotherapy-induced CLDN1 expression may represent a therapeutic opportunity to overcome resistance and improve the outcome of advanced CRC patients.
CELL AND BIOSCIENCE
(2023)
Article
Oncology
Xiaobo Li, Minfeng Chen, Weijin Lu, Jun Tang, Lijuan Deng, Qing Wen, Maohua Huang, Rong Deng, Geni Ye, Wencai Ye, Dongmei Zhang
Summary: This study reveals that FAP alpha is overexpressed in TA-MSCs, leading to secretion of multiple C-C motif chemokine ligands, which promote recruitment of CCR2(+) TAMs and polarization of TAMs into the M2 phenotype, thus facilitating TNBC pulmonary metastasis. The FAP alpha-activated prodrug induces apoptosis in FAP alpha(+) TA-MSCs, suppressing TAM recruitment and polarization, ultimately inhibiting TNBC metastasis. Targeting TA-MSCs with an FAP alpha-activated prodrug emerges as a promising strategy for inhibiting TNBC metastasis.
Article
Biotechnology & Applied Microbiology
Xiangyang Zhang, Min Wang, Junyi Feng, Bin Qin, Chenglin Zhang, Chengshen Zhu, Wentao Liu, Yaohe Wang, Wei Liu, Lei Huang, Shuangshuang Lu, Zhimin Wang
Summary: The development of multidrug resistance (MDR) in cancer chemotherapy is a major challenge. This study identified MVP and BCL2 as potential factors driving MDR in ESCC. A self-assembling nanoparticle platform was designed to deliver Adriamycin and siRNAs targeting MVP and BCL2, reducing drug efflux and promoting apoptosis. The nanoparticles effectively inhibited cancer cell growth and tumor development.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Oncology
John B. Liao, William R. Gwin, Renata R. Urban, Katie M. Hitchcock-Bernhardt, Andrew L. Coveler, Doreen M. Higgins, Jennifer S. Childs, Hania N. Shakalia, Ron E. Swensen, Sasha E. Stanton, Anna Tinker, Tanya A. Wahl, Richard G. Ancheta, Kathryn F. McGonigle, James Y. Dai, Mary L. Disis, Barbara A. Goff
Summary: The study evaluated the activity and safety of pembrolizumab with carboplatin in recurrent platinum-resistant ovarian cancer, showing that this treatment approach had modest activity and good tolerability. A ratio of peripheral T-cell exhaustion to radiographic tumor burden may help identify patients who are more likely to benefit from this chemoimmunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Hang Ke, Faming Zhang, Jingjing Wang, Lingxin Xiong, Xiaoyu An, Xiaolong Tu, Cen Chen, Yueying Wang, Binchen Mao, Sheng Guo, Cunxiang Ju, Xiangfei He, Ruilin Sun, Lei Zhang, Owen A. O'Connor, Qi-Xiang Li
Summary: Both PD1/PD-L1 and CD47 blockades have limited activity in most subtypes of NHL, except for NK/T-cell lymphoma. The hemotoxicity of anti-CD47 agents in clinic may explain their limitations. In this study, a bispecific antibody HX009 was developed, targeting PD1 and CD47, with weakened CD47 binding to reduce toxicity. In vitro and in vivo experiments demonstrated the antitumor activity of HX009, especially in lymphomas with upregulated CD47. These findings support further clinical development of HX009 for NHL treatment.
SCIENTIFIC REPORTS
(2023)
Review
Oncology
Aisha Farhana, Abdullah Alsrhani, Yusuf Saleem Khan, Zafar Rasheed
Summary: Cancer is a major killer with limited targetability, specificity, solubility, and side effects in current diagnostic and therapeutic methods. The complex tumor microenvironments and mitochondrial bioenergetics play significant roles in cancer progression. Nanoparticle-based smart systems have gained momentum due to their high targetability and lower toxicity, and hold great potential in enhancing cancer chemotherapeutics.
Review
Biochemistry & Molecular Biology
Henrik Franzyk, Soren Brogger Christensen
Summary: Many cancer diseases develop slowly, making traditional chemotherapeutics less effective due to their non-selective toxicity. New approaches like antibody-directed enzyme prodrug therapy and gene-directed enzyme prodrug therapy offer promising solutions for targeted cancer treatment. Targeting toxins with tumor-overexpressed enzymes and unique substrate specificity is also a potential strategy for selective chemotherapy.
Review
Biochemistry & Molecular Biology
Jade S. Miller, Natalie E. Bennett, Julie A. Rhoades
Summary: Resisting therapy remains a major challenge in cancer treatment due to cellular plasticity. The Hedgehog (Hh) signaling pathway plays a significant role in drug resistance and is aberrantly activated in various malignancies. This review summarizes the current understanding of Hh signaling in drug resistance, including non-canonical activation of Gli proteins, gene amplification promoting chemotherapy tolerance, and the use of Hh-targeted drugs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Pharmacology & Pharmacy
Ying Zhang, Rukhsora D. Sultonova, Sung-Hwan You, Yoonjoo Choi, So-young Kim, Wan-Sik Lee, Jihyoun Seong, Jung-Joon Min, Yeongjin Hong
Summary: This study investigated a new treatment approach for solid tumors by conjugating L-Asparaginase with specific molecules and improving its anti-tumor efficacy by altering its structure and stability. The results showed that this approach effectively inhibited tumor growth in cells and animals.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Cell Biology
Yibing Chen, Huan Jin, Yucen Song, Ting Huang, Jun Cao, Qing Tang, Zhengzhi Zou
Summary: Tumor-associated macrophages play a significant role in tumor progression and treatment resistance in solid tumors, leading to the development of promising immunotherapeutic strategies targeting macrophages. Targeting TAMs in combination with conventional therapies has shown to be effective in treating solid tumors. Challenges, obstacles in clinical trials, and future perspectives for TAMs-targeting therapies in various cancers are also discussed in this review.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Immunology
Aparna Chhibber, Lingkang Huang, Hong Zhang, Jialin Xu, Razvan Cristescu, Xiaoqiao Liu, Devan Mehrotra, Judong Shen, Peter M. Shaw, Matthew D. Hellmann, Alexandra Snyder
Summary: This study evaluated the impact of HLA genotypes, heterozygosity, and diversity on the efficacy of pembrolizumab and found no conclusive association between them.
Article
Oncology
Joan Jacob, Liezl E. Francisco, Treena Chatterjee, Zhengdong Liang, Shraddha Subramanian, Qingyun J. Liu, Julie H. Rowe, Kendra S. Carmon
Summary: This study identifies GPR56 as a potential therapeutic target for colorectal cancer and demonstrates the efficacy of a GPR56-targeted ADC in preclinical models. The findings suggest that this ADC approach could be a promising treatment option for a large fraction of colorectal cancer patients.
BRITISH JOURNAL OF CANCER
(2023)
Review
Medicine, Research & Experimental
Wenpan Li, Nicholas Little, Jonghan Park, Cole Alexander Foster, Jiawei Chen, Jianqin Lu
Summary: Nanoparticle drug delivery systems have improved antitumor efficacy, but achieving satisfactory distribution and penetration inside solid tumors, especially in stromal fibrous tumors, remains challenging. Tumor-associated fibroblasts reduce the drug delivery efficiency of nanoparticles, making them attractive targets for enhancing tumor delivery efficiency and efficacy of anticancer agents. Opportunities to summarize the underlying mechanisms of TAFs on obstructing nanoparticle-mediated drug delivery into tumors and discuss nanotherapeutic approaches for effectively targeting TAFs have been extensively explored.
MOLECULAR PHARMACEUTICS
(2021)
Article
Oncology
Zhangyi Luo, Katherine M. Eichinger, Anju Zhang, Song Li
Summary: Recent discoveries in cancer metabolism have identified potential metabolic targets to improve cancer therapy. However, the complexity of metabolic pathways and interactions between tumor cells and immune cells present challenges. Further research is needed to understand the differential effects of metabolic inhibition on cancer cells and immune cells and explore nanotechnology as a potential solution.
Article
Oncology
Rebeca Lozano, Daniela C. Salles, Shahneen Sandhu, Isabel M. Aragon, Heather Thorne, Fernando Lopez-Campos, Jose Rubio-Briones, Ana M. Gutierrez-Pecharroman, Laneisha Maldonado, Tomas di Domenico, Alejandro Sanz, Juan D. Prieto, Isabel Garcia, Maria Pacheco, Teresa Garces, Casilda Llacer, Nuria Romero-Laorden, Francisco Zambrana, Pedro P. Lopez-Casas, David Lorente, Joaquin Mateo, Colin C. Pritchard, Emmanuel S. Antonarakis, David Olmos, Tamara L. Lotan, Elena Castro
Summary: While no association was found between gBRCA2 mutations and IDC or CRIB histologies in prostate cancer, bi-allelic BRCA2 loss in primary prostate tumors was significantly associated with both variant morphologies independently of other clinical-pathologic factors.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Oncology
Rebeca Lozano, David Lorente, Isabel M. Aragon, Nuria Romero-Laorden, Paz Nombela, Joaquim Mateo, Alison H. M. Reid, Ylenia Cendon, Diletta Bianchini, Casilda Llacer, Shahneen K. Sandhu, Adam Sharp, Pasquale Rescigno, Teresa Garces, Maria I. Pacheco, Penelope Flohr, Christophe Massard, Pedro P. Lopez-Casas, Elena Castro, Johann S. de Bono, David Olmos
Summary: CTC enumeration and changes following treatment have shown superiority over PSA response in determining the outcome of mCRPC patients receiving AR signaling inhibitors but not taxanes. Early changes in CTCs were found to be better predictors of overall survival in mCRPC patients treated with docetaxel compared to PSA response endpoints.
Article
Biology
Leire Egia-Mendikute, Alexandre Bosch, Endika Prieto-Fernandez, So Young Lee, Borja Jimenez-Lasheras, Ana Garcia del Rio, Asier Antonana-Vildosola, Chiara Bruzzone, Maider Bizkarguenaga, Nieves Embade, Ruben Gil-Redondo, Maria Luz Martinez-Chantar, Marcos Lopez-Hoyos, Nicola G. A. Abrescia, Jose M. Mato, Oscar Millet, Asis Palazon
Summary: Egia-Mendikute et al. have developed a multiplexed flow cytometric bead array to detect antibodies reactive to three immunogenic SARS-CoV-2 proteins simultaneously. This assay is more sensitive than ELISA and has superior potential to detect low antibody titers, even in COVID-19-negative individuals.
COMMUNICATIONS BIOLOGY
(2021)
Article
Immunology
Endika Prieto-Fernandez, Leire Egia-Mendikute, Laura Vila-Vecilla, Alexandre Bosch, Adrian Barreira-Manrique, So Young Lee, Ana Garcia-del Rio, Asier Antonana-Vildosola, Borja Jimenez-Lasheras, Leire Moreno-Cugnon, Jesus Jimenez-Barbero, Edurne Berra, June Ereno-Orbea, Asis Palazon
Summary: Hypoxia decreases the attachment of SARS-CoV-2 virus to epithelial cells, inhibiting the infection rate; furthermore, hypoxia affects the binding of spike protein to cells by reducing the cell surface HS levels; hypoxia or loss of HS-related proteins can reduce the binding of the virus to host cells.
EMERGING MICROBES & INFECTIONS
(2021)
Article
Engineering, Biomedical
Juan Carlos Gil-Redondo, Andreas Weber, Barbara Zbiral, Maria dM. Vivanco, Jose L. Toca-Herrera
Summary: Cells can sense the stiffness of their surroundings and adjust their mechanical properties accordingly. MCF-7 breast cancer cells demonstrate the ability to detect and respond to substrate stiffness, leading to changes in their stiffness and viscosity.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2022)
Article
Biochemistry & Molecular Biology
Nivetha Krishna Moorthy, Oliver Seifert, Stephan Eisler, Sara Weirich, Roland E. Kontermann, Markus Rehm, Gavin Fullstone
Summary: The study investigated the effectiveness of antibody-based fusion proteins combining hexavalent TRAIL and ANG2 for GBM treatment, demonstrating potent induction of apoptosis. However, low TRAIL receptor expression on the blood-brain barrier endothelial cells interfered with efficient transport of the fusion proteins. Therapeutic strategies may need to include combinatorial approaches, such as TRAIL-R masking, to achieve effective CNS transport.
Article
Oncology
Nadine Aschmoneit, Katharina Kocher, Martin Siegemund, Martina S. Lutz, Lennart Kuhl, Oliver Seifert, Roland E. Kontermann
Summary: Targeting costimulatory receptors of the TNFSF to activate T-cells and promote anti-tumor T-cell function has potential in cancer immunotherapy. Dual-acting costimulatory molecules, formed by combining different members of the TNFSF, can activate two different receptors on cells. Incorporating TNF superfamily costimulatory ligands into a dual-acting molecule enhances T-cell proliferation and anti-tumor activity.
Article
Medicine, Research & Experimental
Lennart Kuehl, Nadine Aschmoneit, Roland E. Kontermann, Oliver Seifert
Summary: This study presents a novel approach to solve the light-chain problem in the generation of bispecific antibodies by using genetically modified IgE domains. The researchers successfully generated bispecific antibodies with heterodimerization capabilities and demonstrated their versatility and efficacy in various applications.
Article
Biochemistry & Molecular Biology
Oliver Seifert, Roland E. Kontermann
Summary: In this study, two different PEG mimetic approaches, GlycoTAIL and FlexiTAIL, were used to increase the hydrodynamic radius of antibody fragments and improve their pharmacokinetic properties. The modified proteins exhibited prolonged half-life and increased drug disposition in mice without compromising stability and antigen binding. The FlexiTAIL sequence of 248 residues had the strongest effect, suggesting that it is a flexible and modular system for improving protein pharmacokinetics.
Article
Oncology
Jose A. Lopez-Ruiz, Jon A. Mieza, Ignacio Zabalza, Maria D. M. Vivanco
Summary: This study compares the results of pathological and molecular subtyping in breast cancer patients and finds discrepancies between the two. The study suggests that traditional clinical pathological classification may lead to unnecessary or inadequate treatment for some patients. Therefore, molecular subtyping should be used in conjunction with clinical pathological classification to design precise treatment regimens for patients with early breast cancer.
Article
Cell Biology
Konstantin Stoletov, Saray Sanchez, Irantzu Gorrono, Miriam Rabano, Maria d. M. Vivanco, Robert Kypta, John D. Lewis
Summary: Using a unique intravital imaging platform and fluorescent reporters, researchers visualised the activities of D-catenin/TCF-dependent and ATF2-dependent signalling during cancer cell invasion, intravasation and metastatic lesion formation. They found that cancer cells easily shifted between low and high canonical Wnt activity states. Cancer cells with low Wnt canonical activity showed higher invasion and intravasation potential, while cancer cells with low ATF2-dependent activity were less invasive. Simultaneous visualisation of both reporters confirmed their complementary activities in primary tumours and metastatic lesions. These findings may inform the development of targeted therapies for different stages of metastasis by targeting different branches of Wnt signalling.
JOURNAL OF CELL SCIENCE
(2023)
Article
Medicine, Research & Experimental
Lennart Kuehl, Annelie K. Schaefer, Sebastian Kraft, Nadine Aschmoneit, Roland E. Kontermann, Oliver Seifert
Summary: Bispecific antibodies are molecules that have versatile modes of action and applications for therapy. They are commonly developed as T-cell engagers (TCE), which simultaneously target an antigen expressed by tumor cells and CD3 expressed by T-cells, thereby inducing T-cell-mediated target cell killing. There is growing evidence that the molecular composition and valency for the target antigen influence the activity of TCEs.
Article
Multidisciplinary Sciences
Andreas Weber, Maria D. M. Vivanco, Jose L. Toca-Herrera
Summary: Cell mechanical properties can be used as label free markers for disease diagnosis, such as cancer. Atomic Force Microscopy (AFM) is commonly used to study cell mechanics, but requires skilled users, physical modeling, and data interpretation expertise. Recently, machine learning and artificial neural network techniques have been used to automatically classify AFM datasets. We propose the use of self-organizing maps (SOMs) as unsupervised artificial neural networks to analyze mechanical measurements on breast cancer cells treated with different substances that affect estrogen receptor signaling.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Ana Garcia-del Rio, Endika Prieto-Fernandez, Leire Egia-Mendikute, Asier Antonana-Vildosola, Borja Jimenez-Lasheras, So Young Lee, Adrian Barreira-Manrique, Samanta Romina Zanetti, Ander de Blas, Paloma Velasco-Beltran, Alexandre Bosch, Ana M. Aransay, Asis Palazon
Summary: Factor-inhibiting HIF (FIH) is an asparagine hydroxylase expressed in tumors, and its deletion may lead to increased metabolism, decreased proliferation, and increased immune infiltration in cancer cells.
Meeting Abstract
Gastroenterology & Hepatology
Claudia Gil-Pitarch, Esther Bertran, Iker Uriarte, Natalia Herman-Sanchez, Jose Manuel Garcia-Heredia, Naroa Goikoetxea, Marina Serrano-Macia, Ruben Rodriguez Agudo, Sofia Lachiondo-Ortega, Maria Mercado-Gomez, Miriam Rabano, Teresa Cardoso Delgado, Jorge Simon Espinosa, Luis Alfonso Martinez-Cruz, Cesar Augusto Martin, Maria Vivanco, Matias A. Avila, Manuel Gahete Ortiz, Isabel Fabregat, Amancio Carnero, Maria Luz Martinez-Chantar
JOURNAL OF HEPATOLOGY
(2022)