Review
Biochemistry & Molecular Biology
Lulin Ma, Wenjing Zhao, Shiqian Huang, Feng Xu, Yafeng Wang, Daling Deng, Tianhao Zhang, Shaofang Shu, Xiangdong Chen
Summary: Pain, an important problem in medicine and public health, has significant research significance. Opioids are currently the main drugs used to relieve pain, but their use is limited due to obvious side effects. Therefore, there is an urgent need to develop new drugs for pain relief. Multiple studies have shown that the IGF/IGF-1R pathway plays a crucial role in the occurrence and development of pain. This review summarizes and discusses the therapeutic potential of the IGF/IGF-1R signal pathway for pain. It also highlights the regulation of pain by IGF/IGF-1R through actions on neuronal excitability, neuroinflammation, glial cells, apoptosis, and more. However, further research is still needed to fully understand the mechanisms of pain occurrence and development. In conclusion, while more in-depth studies are required, these findings suggest that the IGF/IGF-1R signal pathway holds promise as a therapeutic target for pain.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Oncology
Upendra K. Soni, Liam Jenny, Rashmi S. Hegde
Summary: The insulin-like growth factor receptor (IGF-1R) has been extensively studied as a potential target in oncology, but the initial promise has not been fulfilled due to resistance mechanisms and toxicities. Lack of patient stratification based on biomarkers in previous clinical trials has been recognized as a limitation. There is now growing interest in revisiting IGF-1R targeted therapeutics with predictive biomarker-driven patient stratification. The sub-cellular localization of IGF-1R has emerged as a potential biomarker.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Yu-Tzu Chan, Ruey-Jen Lin, Ya-Hui Wang, Tsai-Hsien Hung, Yenlin Huang, John Yu, Jyh-Cherng Yu, Alice L. Yu
Summary: This study reveals the crucial role of YAP in breast cancer stem cells. Knockdown of YAP reduces the viability and stemness of BCSCs in vitro and tumor formation in vivo. IGF-1R and IGF-1 regulate the expression and localization of YAP, and YAP overexpression increases the expression of IGF-1. Clinical analysis shows that high levels of YAP and IGF-1 are associated with shorter overall survival in basal-like breast cancer patients. In conclusion, the interplay between YAP and the IGF-1/IGF-1R pathway is clinically relevant for sustaining the properties of BCSCs.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Oncology
Yinqi Zhang, Chengqi Gao, Fei Cao, Ying Wu, Shuanggang Chen, Xue Han, Jingqin Mo, Zhiyu Qiu, Weijun Fan, Penghui Zhou, Lujun Shen
Summary: IGF-1 and IGF-1R show inconsistent gene expression levels in various cancer cell lines, with high expression typically detected in most malignant tumors. High expression of IGF-1 is closely associated with unfavorable overall survival in BLCA, CHOL, and LAML patients, while high expression of IGF-1R is closely linked to poor overall survival in BLCA, LIHC, and LUAD patients.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Panpan Wang, Victor C. Y. Mak, Lydia W. T. Cheung
Summary: The insulin-like growth factor (IGF) axis plays important roles in cancer development and metastasis. The type 1 IGF receptor (IGF-1R) is a key member in the IGF axis and has been recognized for its oncogenic role in multiple cancer lineages. This article reviews the occurrence of IGF-1R aberrations and activation mechanisms in cancers, and discusses the available therapeutic agents for IGF-1R inhibition, including antisense oligonucleotide, tyrosine kinase inhibitors, and monoclonal antibodies. Combination therapy targeting IGF-1R and other oncogenic vulnerabilities has shown promise, and new concepts such as blockage of nuclear translocation of IGF-1R are being explored to improve therapeutic efficacy.
Article
Cell Biology
Maria Dobre, Vlad Herlea, Catalina Vladut, Mihai Ciocirlan, Vasile Daniel Balaban, Gabriel Constantinescu, Mircea Diculescu, Elena Milanesi
Summary: The study identified a panel of downregulated miRNAs in PDAC tissue, which could serve as potential therapeutic targets for the development of new miRNA-based therapies for PDAC.
Article
Cell Biology
Ming Xiu, Xia Huan, Yang Ou, Sha Ying, Jianmeng Wang
Summary: The study investigated the cellular behavior and characteristics of IGF-1/IGF-1R in intestinal cells, revealing that IGF-1 can internalize into the cytoplasm and transport into the cell nuclei. It was found that IGF-1R undergoes clathrin-mediated endocytosis and enters into Rab-5-positive endosomes before being transported to the cell nuclei along microtubules, promoting cell proliferation.
CELL PROLIFERATION
(2021)
Article
Cell Biology
Xinyu Wang, Pengcheng Zhou, Liangxin Lin, Bo Wu, Zhaoyu Fu, Xing Huang, Dong Zhu
Summary: IGF-1R inhibitors have been identified as a promising drug target for Ewing sarcoma. In this study, compounds capable of inhibiting IGF-1R function were screened using virtual technology. Two potential inhibitors, ZINC000014946303 and ZINC000006003042, were found with high binding affinity to IGF-1R. These compounds showed good toxicity profiles and could serve as a direction for future IGF-1R inhibitor development.
Review
Biochemistry & Molecular Biology
Syuan-Ling Lin, Chih-Yang Lin, Wei Lee, Chiao-Fang Teng, Woei-Cherng Shyu, Long-Bin Jeng
Summary: This review focuses on the role of IGF/IGF-1R signaling in cancer initiation and proliferation, maintenance of stem cell characteristics, and enhancement of stem cell-based therapeutics. It summarizes the current progress in preclinical IGF-targeted therapies and the function of IGF/IGF-1R signaling in stem cell self-renewal and regenerative medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Yongsheng Liu, Shengze Yu, Tianqi Xu, Vitalina Bodenko, Anna Orlova, Maryam Oroujeni, Sara S. Rinne, Vladimir Tolmachev, Anzhelika Vorobyeva, Torbjorn Graslund
Summary: This study evaluated the use of Ga-68 and In-111-labeled affibody construct NODAGA-(HE)(3)-Z(IGF-1R:4551) for the imaging of IGF-1R expression using PET and SPECT techniques. The results showed that these imaging probes could specifically bind to IGF-1R both in vitro and in vivo, demonstrating their potential for visualizing IGF-1R expression in malignant tumors.
Article
Oncology
Han Koo, Sangwon Byun, Jieun Seo, Yuri Jung, Dong Chul Lee, Jung Hee Cho, Young Soo Park, Young Il Yeom, Kyung Chan Park
Summary: IGF-1R is commonly overexpressed in solid tumors, but gene amplification is rare. Research shows that PKM2 regulates IGF-1R protein expression by stabilizing the precursor protein through HSP90 binding. Inhibiting PKM2 reduces IGF-1R levels, inhibits AKT activation, and increases apoptotic cell death, suggesting PKM2 as a potential therapeutic target in cancers with dysregulated IGF signaling.
Article
Anatomy & Morphology
Cemile Merve Seymen, Atiye Seda Yar Saglam, Zubeyir Elmazoglu, Gokce Nur Arik, Gulnur Take Kaplanoglu
Summary: The study investigated the involvement of endometrial IGF-1R/IGF-1/Bcl-2 pathways and the potential regulatory effects of exogenously administered melatonin in PCOS. Results showed that melatonin administration could reverse the morphological changes induced by polycystic ovary induction.
Article
Agriculture, Dairy & Animal Science
Junyan Bai, Xinle Wang, Jingyun Li, Longwei Wang, Hongdeng Fan, Mengke Chen, Fanlin Zeng, Xiaoning Lu, Yuhan He
Summary: This study investigated the association between single nucleotide polymorphisms (SNPs) of the IGF-1R gene and egg quality and carcass traits in quails. Two SNPs (A57G and A72T) were found in three quail strains, with A57G associated with yolk width in one strain and A72T associated with egg shell thickness and other egg traits in different strains. Haplotypes based on the two SNPs also had significant effects on egg shell thickness and egg weight in the quail strains. Additionally, A72T was associated with liver weight and dressing percentage in all three strains. The IGF-1R gene may serve as a molecular genetic marker for improving egg quality and carcass traits in quails.
Article
Biochemistry & Molecular Biology
Baoliang Guo, Zheng Lv, Chunguo Cui, Wan Wang
Summary: This study found that IGF-1/IGF-1R can be internalized into the cytoplasm in breast cancer cells, and IGF-1R can also enter cell nuclei under the mediation of IGF-1, with nuclear-localized IGF-1R having important potential biological effects related to the proliferation of breast cancer cells.
CELL BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Cell & Tissue Engineering
Rongrong Jiang, Miao Wang, Xiaobo Shen, Shuai Huang, Jianpeng Han, Lei Li, Zhiliang Xu, Chengfeng Jiang, Qiao Zhou, Xingmei Feng
Summary: The study demonstrated that SUMO1 modification of IGF-1R inhibited osteogenic differentiation of PDLSCs by binding to SNAI2 in a high glucose environment, potentially a key factor leading to alveolar bone loss in diabetic patients. Adding IGF-1R inhibitors to high glucose osteogenic medium enhanced osteogenic differentiation of PDLCSs, offering potential new hope for alveolar bone regeneration in diabetic patients.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Oncology
S. Novello, V Torri, C. Grohe, S. Kurz, M. Serke, T. Wehler, A. Meyer, D. Ladage, M. Geissler, I Colantonio, C. Cauchi, E. Stoelben, A. Ceribelli, C. Kropf-Sanchen, G. Valmadre, G. Borra, M. Schena, A. Morabito, A. Santo, V Gregorc, R. Chiari, M. Reck, G. Schmid-Bindert, G. Folprecht, F. Griesinger, A. Follador, P. Pedrazzoli, A. Bearz, O. Caffo, N. J. Dickgreber, L. Irtelli, G. Wiest, V Monica, L. Porcu, C. Manegold, G. Scagliotti
Summary: This study aimed to evaluate the predictive utility of ERCC1 and TS mRNA expression levels in resected tumors. The results showed that tailored adjuvant chemotherapy in completely resected stage II-III NSCLC demonstrated a non-statistically significant trend for overall survival favoring the tailored arm, with better efficacy/toxicity ratio compared to standard chemotherapy.
ANNALS OF ONCOLOGY
(2022)
Correction
Oncology
S. Novello, V. Torri, C. Grohe, S. Kurz, M. Serke, T. Wehler, A. Meyer, D. Ladage, M. Geissler, I. Colantonio, C. Cauchi, E. Stoelben, A. Ceribelli, C. Kropf-Sanchen, G. Valmadre, G. Borra, M. Schena, A. Morabito, A. Santo, V. Gregorc, R. Chiari, M. Reck, G. Schmid-Bindert, G. Folprecht, F. Griesinger, A. Follador, P. Pedrazzoli, A. Bearz, O. Caffo, N. J. Dickgreber, L. Irtelli, G. Wiest, V. Monica, L. Porcu, C. Manegold, G. V. Scagliotti
ANNALS OF ONCOLOGY
(2022)
Review
Oncology
Marco Tagliamento, Paolo Bironzo, Hubert Curcio, Emmanuele De Luca, Daniele Pignataro, Simonetta G. Rapetti, Marco Audisio, Valentina Bertaglia, Chiara Paratore, Maristella Bungaro, Emanuela Olmetto, Elisa Artusio, Maria Lucia Reale, Clizia Zichi, Enrica Capelletto, Simona Carnio, Lucio Buffoni, Francesco Passiglia, Silvia Novello, Giorgio Vittorio Scagliott, Massimo Di Mai
Summary: Research has shown that anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs) may be a treatment option for chemotherapy-resistant asMM, although reliable predictive factors are currently lacking.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Article
Oncology
Arlene O. Siefker-Radtke, Andrea Necchi, Se Hoon Park, Jesus Garcia-Donas, Robert A. Huddart, Earle F. Burgess, Mark T. Fleming, Arash Rezazadeh Kalebasty, Begona Mellado, Sergei Varlamov, Monika Joshi, Ignacio Duran, Scott T. Tagawa, Yousef Zakharia, Sydney Akapame, Ademi E. Santiago-Walker, Manish Monga, Anne O'Hagan, Yohann Loriot
Summary: This study evaluated the long-term efficacy and safety of Erdafitinib in patients with locally advanced or metastatic urothelial carcinoma. The results showed consistent activity and manageable safety profile in these patients.
Review
Oncology
Jordi Remon, Benjamin Lacas, Roy Herbst, Martin Reck, Edward B. Garon, Giorgio V. Scagliotti, Rodryg Ramlau, Nasser Hanna, Johan Vansteenkiste, Kiyotaka Yoh, Harry J. M. Groen, John V. Heymach, Sumithra J. Mandrekar, Isamu Okamoto, Joel W. Neal, Rebecca S. Heist, David Planchard, Jean-Pierre Pignon, Benjamin Besse
Summary: This study validates the efficacy of combining angiogenesis inhibitors with second-line treatment in advanced non-small cell lung cancer (NSCLC) patients, showing significant improvements in overall survival and progression-free survival, particularly in younger patients and those who started the first-line therapy more recently.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Marika Sculco, Marta La Vecchia, Anna Aspesi, Giulia Pinton, Michela G. Clavenna, Elisabetta Casalone, Alessandra Allione, Federica Grosso, Roberta Libener, Alberto Muzio, Ottavio Rena, Guido Baietto, Sara Parini, Renzo Boldorini, Daniela Giachino, Mauro Papotti, Giorgio Scagliotti, Enrica Migliore, Dario Mirabelli, Laura Moro, Corrado Magnani, Daniela Ferrante, Giuseppe Matullo, Irma Dianzani
Summary: This study aimed to search for new predisposing genes and assess the prevalence of pathogenic variants (PVs) in DNA repair genes in 113 unselected patients with malignant pleural mesothelioma (MPM), and evaluate the sensitivity of these patients to tailored treatments. The researchers identified PVs in approximately 7% of the MPM patients, mainly in genes involved in DNA repair. In vitro studies showed that a specific treatment induced apoptosis in MPM cells with DNA repair insufficiency. These findings suggest the potential benefits of personalized treatments for MPM patients with DNA repair defects.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Iris Chiara Salaroglio, Dimas Carolina Belisario, Paolo Bironzo, Preeta Ananthanarayanan, Luisa Ricci, Sabrina Digiovanni, Simona Fontana, Francesca Napoli, Alberto Sandri, Chiara Facolmata, Roberta Libener, Valentina Comunanza, Federica Grosso, Elena Gazzano, Francesco Leo, Riccardo Taulli, Federico Bussolino, Luisella Righi, Mauro Giulio Papotti, Silvia Novello, Giorgio Vittorio Scagliotti, Chiara Riganti, Joanna Kopecka
Summary: The neddylation inhibitor MLN4924 and cisplatin combination has anti-tumor effects in malignant pleural mesothelioma (MPM) by blocking the SCF complex activity and triggering endoplasmic reticulum stress-induced immunogenic cell death (ICD). SKP2 is identified as a new stratification marker for sensitivity to cisplatin and drugs interfering with ubiquitination/proteasome systems in MPM.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Andrew G. Nicholson, Ming S. Tsao, Mary Beth Beasley, Alain C. Borczuk, Elisabeth Brambilla, Wendy A. Cooper, Sanja Dacic, Deepali Jain, Keith M. Kerr, Sylvie Lantuejoul, Masayuki Noguchi, Mauro Papotti, Natasha Rekhtman, Giorgio Scagliotti, Paul van Schil, Lynette Sholl, Yasushi Yatabe, Akihiko Yoshida, William D. Travis
Summary: The 2021 WHO Classification of Thoracic Tumours focuses on the application of genetics and molecular pathology, providing specific classifications and diagnostic criteria for various tumors, while emphasizing new tumor features and concepts.
JOURNAL OF THORACIC ONCOLOGY
(2022)
Review
Cell Biology
Antonio Ungaro, Marcello Tucci, Alessandro Audisio, Lavinia Di Prima, Chiara Pisano, Fabio Turco, Marco Donatello Delcuratolo, Massimo Di Maio, Giorgio Vittorio Scagliotti, Consuelo Buttigliero
Summary: Significant progress has been made in understanding the biology of tumor progression in urothelial carcinoma (UC) in recent decades. Although the introduction of immune checkpoint inhibitors has changed the therapeutic landscape, advanced UC still has poor survival rates. This review summarizes the mechanism of action of antibody drug conjugates (ADCs), their applications in UC, and future perspectives in clinical practice.
Review
Oncology
Benoit Cadieux, Robert Coleman, Pegah Jafarinasabian, Allan Lipton, Robert Z. Orlowski, Fred Saad, Giorgio Scagliotti, Kazuyuki Shimizu, Alison Stopeck
Summary: Denosumab is an effective medication for preventing complications of bone metastases in patients with multiple myeloma and solid tumors. It reduces the risk of skeletal-related events and improves pain outcomes. Although there are rare but serious toxicities associated with denosumab, its convenient dosing schedule and clinical efficacy make it a valuable option for SRE prevention.
JOURNAL OF BONE ONCOLOGY
(2022)
Article
Oncology
G. Procopio, V. E. Chiuri, M. Giordano, A. R. Alitto, R. Maisano, R. Bordonaro, S. Cinieri, S. Rossetti, S. De Placido, M. Airoldi, L. Galli, D. Gasparro, G. M. Ludovico, P. F. Guglielmini, C. Carella, P. Nova, M. Aglietta, L. Schips, P. Beccaglia, A. Sciarra, L. Livi, D. Santini
Summary: Limited real-world data exist on the effectiveness and safety of abiraterone acetate plus prednisone (abiraterone hereafter) in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) naive to chemotherapy. Most of the few available studies had a retrospective design and included a small number of patients. In the interim analysis of the ABItude study, abiraterone showed good clinical effectiveness and safety profile in the chemotherapy-naive setting over a median follow-up of 18 months. Patients and methods: We evaluated clinical and patient-reported outcomes (PROs) of chemotherapy-naive mCRPC patients treated with abiraterone as for clinical practice in the Italian, observational, prospective, multicentric ABItude study. mCRPC patients were enrolled at abiraterone start (February 2016-June 2017) and followed up for 3 years; clinical endpoints and PROs, including quality of life (QoL) and pain, were prospectively collected. Kaplan-Meier curves were estimated. Results: Of the 481 patients enrolled, 454 were assessable for final study analyses. At abiraterone start, the median age was 77 years, with 58.6% elderly patients and 69% having at least one comorbidity (57.5% cardiovascular diseases). Visceral metastases were present in 8.4% of patients. Over a median follow-up of 24.8 months, median progression-free survival (any progression reported by the investigators), time to abiraterone discontinuation, and overall survival were, respectively, 17.3 months [95% confidence interval (CI) 14.1-19.4 months], 16.0 months (95% CI 13.1-18.2 months), and 37.3 months (95% CI 36.5 months-not estimable); 64.2% of patients achieved >= 50% reduction in prostate-specific antigen. QoL assessed by Functional Assessment of Cancer Therapy-Prostate, the European Quality of Life 5 Dimensions 3 Level, and European Quality of Life Visual Analog Scale remained stable during treatment. Median time to pain progression according to Brief Pain Inventory data was 31.1 months (95% CI 24.8 months-not estimable). Sixty-two patients (13.1%) had at least one adverse drug reaction (ADR) and 8 (1.7%) one serious ADR. Conclusion: With longer follow-up, abiraterone therapy remains safe, well tolerated, and active in a large unselected population.
Review
Biochemistry & Molecular Biology
Maristella Bungaro, Francesco Passiglia, Giorgio Scagliotti
Summary: Compared to the general population, lung cancer patients have a higher risk of COVID-19 infection and experience diagnostic delays and higher mortality rates. Professional organizations have provided new recommendations for the clinical management of lung cancer patients during the pandemic, including the use of telemedicine for non-urgent consultations and temporary suspension of screening programs. The vaccine campaign has emerged as a main strategy to combat the COVID-19 pandemic, offering hope for lung cancer patients.
Review
Oncology
Irene Persano, Elena Parlagreco, Anna La Salvia, Marco Audisio, Marco Volante, Consuelo Buttigliero, Giorgio Vittorio Scagliotti, Maria Pia Brizzi
Summary: The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may be a rare coincidence or a manifestation of von Hippel-Lindau disease (VHL). Diagnosing the differential between panNET and RCC pancreatic metastasis is challenging due to their similar radiological and cytopathological features. Proper differential diagnosis and therapeutic algorithms are crucial to determine the appropriate treatment. This review collected cases of concurrent panNET and RCC diagnosis from literature, providing insight and guidance for differential diagnosis and treatment.
SEMINARS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Irene Persano, Massimiliano Cani, Benedetta Del Rio, Giorgia Ferrari, Edoardo Garbo, Elena Parlagreco, Chiara Pisano, Valeria Cetoretta, Marco Donatello Delcuratolo, Fabio Turco, Alessandro Audisio, Cristina Cecchi, Gianmarco Leone, Valerio Maria Napoli, Valentina Bertaglia, Valentina Bianco, Enrica Capelletto, Carmen D'Amiano, Massimo Di Maio, Martina Gianetta, Silvia Novello, Francesco Passiglia, Giorgio Vittorio Scagliotti, Paolo Bironzo
Summary: This study reports the side effects, adverse events, and patient-reported outcomes following administration of the BNT162b2 vaccine in cancer patients. The results show that BNT162b2 is safe in the short-term for cancer patients and has a positive impact on quality of life.
Article
Respiratory System
Daphne W. Dumoulin, Paolo Bironzo, Francesco Passiglia, Giorgio V. Scagliotti, Joachim G. J. V. Aerts
Summary: Despite the progress in immunotherapy outcomes in various malignancies, its benefits are limited in small cell lung cancer, malignant pleural mesothelioma, and thymic epithelial tumors. This review provides a comprehensive overview of the clinical presentation, diagnosis, staging, pathophysiology, and treatment options for these rare thoracic cancers. It also explores opportunities for further improving therapies.
EUROPEAN RESPIRATORY REVIEW
(2023)
