Article
Oncology
Yalun Li, Ke Wang, Panwen Tian, Weimin Li
Summary: MET gene fusions are rare in non-small cell lung cancer, but a patient was found to have the MET-DSTN fusion gene after developing resistance. The patient achieved a positive clinical response after receiving combined treatment with MET inhibitors and EGFR-TKIs.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
Chuangzhou Rao, Liangqin Nie, Xiaokang Wu, Xiaobo Miao, Ting Chen, Liuxi Chen, Dongqing Zhang, Quan Lin
Summary: This study reports two cases of NSCLC patients who acquired the ALK C1156F mutation during treatment with crizotinib. Both patients achieved prolonged progression-free survival after subsequent treatment with alectinib. This is the first clinical evidence that NSCLC patients harboring the acquired ALK C1156F mutation are resistant to crizotinib but sensitive to alectinib.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Anna M. Schlafli, Igor Tokarchuk, Sarah Parejo, Susanne Jutzi, Sabina Berezowska, Nikolai Engedal, Mario P. Tschan
Summary: The study shows that ALK inhibition induces LC3B-independent macroautophagic flux in EML4-ALK(+) cells to support cancer cell survival and clonogenic growth.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Jiaye Lu, Jingwei Li, Ziyou Lin, Huaxuan Li, Linlin Lou, Wen Ding, Shumin Ouyang, Yonghui Wu, Yuanzhen Wen, Xiaobing Chen, Peibin Yue, Yuanxiang Wang, Peiqing Liu, Jinjian Lu, Jian Zhang, Weineng Feng, Xiaolei Zhang
Summary: This study revealed the role of tumor-associated macrophages (TAMs) in acquired drug resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung cancer. M2-like reprogramming of TAMs and reduced phagocytosis were observed in gefitinib-resistant lung cancer cells. CD47 upregulation in TKI-resistant cells enhanced M2 macrophage polarization and cancer cell escape from macrophage phagocytosis. Inhibition of STAT3 alleviated the acquired resistance to EGFR-TKIs by inhibiting the CD47-SIRP alpha signaling axis and M2 polarization.
Article
Pharmacology & Pharmacy
Yue Zeng, Yuanqing Feng, Guihua Fu, Junlan Jiang, Xiaohan Liu, Yue Pan, Chunhong Hu, Xianling Liu, Fang Wu
Summary: The acquired resistance of EGFR-TKIs is inevitable and heterogeneous. Osimertinib is the standard second-line therapy for T790M-positive patients, but its efficacy in patients with concurrent multiple driver gene resistance is unclear. The T790M accompanying other driver gene resistance will be a new subtype, requiring new treatment options.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chia-Hung Chen, Bo-Wei Wang, Yu-Chun Hsiao, Chun-Yi Wu, Fang-Ju Cheng, Te-Chun Hsia, Chih-Yi Chen, Yihua Wang, Zhang Weihua, Ruey-Hwang Chou, Chih-Hsin Tang, Yun-Ju Chen, Ya-Ling Wei, Jennifer L. Hsu, Chih-Yen Tu, Mien-Chie Hung, Wei-Chien Huang
Summary: Upregulation of active sodium/glucose co-transporter 1 (SGLT1) was found to confer the development of acquired EGFR TKI resistance and was correlated with poorer clinical outcomes in NSCLC patients. Blockade of SGLT1 overcame this resistance by reducing glucose uptake in NSCLC cells, suggesting a potential strategy to improve the therapeutic efficacy of EGFR TKIs in NSCLC patients.
Article
Oncology
Chaelin Lee, Miso Kim, Dong-Wan Kim, Tae Min Kim, Soyeon Kim, Sun-Wha Im, Yoon Kyung Jeon, Bhumsuk Keam, Ja-Lok Ku, Dae Seog Heo
Summary: This study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR tyrosine kinase inhibitors (TKIs), but is sensitive to 3rd generation EGFR TKIs. In addition, the study identifies that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.
CANCER RESEARCH AND TREATMENT
(2022)
Article
Oncology
Marianne Oulhen, Patrycja Pawlikowska, Tala Tayoun, Marianna Garonzi, Genny Buson, Claudio Forcato, Nicolo Manaresi, Agathe Aberlenc, Laura Mezquita, Yann Lecluse, Pernelle Lavaud, Charles Naltet, David Planchard, Benjamin Besse, Francoise Farace
Summary: Gatekeeper mutations are only identified in 50% of cases at resistance to ALK-TKIs. Circulating tumor cells (CTCs) are useful tools in identifying additional resistance mechanisms and can be sequenced at the single-cell level. Comprehensive analysis of CTCs reveals wide copy number alteration (CNA) heterogeneity and high chromosomal instability (CIN) at resistance to ALK-TKIs, providing valuable insights for precision medicine and overcoming resistance to ALK-targeted therapies.
NPJ PRECISION ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
M. A. Berry, A. R. Bland, J. C. Ashton
Summary: Lung cancer is a major cause of cancer-related deaths. Co-targeting ALK and SHP2 may be an effective strategy for improving drug efficacy. The combination of a SHP2 inhibitor and alectinib can significantly and synergistically suppress the growth of ALK-positive lung cancer cells by regulating the cell cycle and inducing apoptosis.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Ke-Ren Zhang, Yu-Fei Zhang, Hui-Min Lei, Ya-Bin Tang, Chun-Shuang Ma, Qian-Ming Lv, Shi-Yi Wang, Li-Ming Lu, Ying Shen, Hong-Zhuan Chen, Liang Zhu
Summary: The study uncovered a metabolic mechanism driving resistance to EGFR TKIs by promoting cystine metabolism, and suggested AKR1B1 as a potential therapeutic target to overcome resistance to EGFR TKIs.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Wen-Jing Liu, Lin Wang, Feng-Mei Zhou, Shu-Wen Liu, Wei Wang, Er-Jiang Zhao, Quan-Jun Yao, Wei Li, Yan-Qiu Zhao, Zhi Shi, Jian-Ge Qiu, Bing-Hua Jiang
Summary: In this study, it was found that elevated NOX4 expression was associated with acquired resistance to EGFR-TKIs. Knockdown of NOX4 increased sensitivity to gefitinib and osimertinib, while forced expression of NOX4 induced resistance. YY1 and IL-8 were identified as downstream targets of NOX4, regulating PD-L1 expression and TKIs resistance. These molecules may serve as potential biomarkers and therapeutic targets for overcoming TKIs resistance.
DRUG RESISTANCE UPDATES
(2023)
Article
Oncology
Yuxue Xia, Lu Zhang, Wenjuan He, Huaxiong Pan, Jun Fang, Guohui Cui
Summary: This study reported a case of ALK(+) LBCL in which the patient had progressive disease after treatment with crizotinib and chemotherapy, but achieved partial response and remained stable after treatment with alectinib combined with hyper-CVAD, followed by alectinib monotherapy.
CANCER BIOLOGY & THERAPY
(2023)
Article
Multidisciplinary Sciences
Bin Wang, Yang Song, Zhuo Chen, Xiaona Su, Xin Yang, Zhi Wei, Junxia Chen, Chuan Chen, Mengxia Li
Summary: This study aimed to investigate the therapeutic effect and safety of ALK inhibitor in ALK-positive lung cancer patients. A total of 59 patients were recruited and divided into two groups: conventional adjuvant chemotherapy and targeted therapy with crizotinib. The results showed that targeted therapy significantly improved disease-free survival (DFS) and overall survival (OS) compared to adjuvant chemotherapy (P < 0.05). Elevated aspartate transaminase/alanine aminotransferase, nausea, and vomiting were the most common adverse events observed.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Shuye Lin, Hongyun Ruan, Lin Qin, Cong Zhao, Meng Gu, Ziyu Wang, Bin Liu, Haichao Wang, Jinghui Wang
Summary: This study investigated the epigenetic effects of MUC17 in acquired drug-resistant cells of EGFR-TKIs. In gefitinib/osimertinib-resistant (GR/OR) cells, downregulation of MUC17 was mediated by promoter methylation promoted by the DNMT1/UHRF1 complex, leading to activation of NF-kappa B activity. MUC17 acted as an epigenetic sensor for monitoring resistance to EGFR-TKIs in GR/OR cells.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Oncology
Mercedes Herrera-Juarez, Cristina Serrano-Gomez, Helena Bote-de-Cabo, Luis Paz-Ares
Summary: Precision oncology aims to design the best cancer treatment based on tumor biology. In NSCLC, patients with actionable genomic aberrations can benefit from targeted therapy, such as EGFR mutations and ALK rearrangements. Effective inhibitors have been developed for various druggable targets, leading to a paradigm shift in NSCLC treatment.
Editorial Material
Cardiac & Cardiovascular Systems
Pierluigi Novellis, Fabrizio Monaco, Giovanni Landoni, Francesca Rossetti, Angelo Carretta, Vanesa Gregorc, Alberto Zangrillo, Giulia Veronesi
Summary: Cardiovascular comorbidities often prevent patients with resectable early-stage lung cancer from undergoing surgery, but venoarterial extracorporeal membrane oxygenation can provide intraoperative cardiovascular and respiratory support, reducing the risk of complications and allowing potentially curative surgical resection.
ANNALS OF THORACIC SURGERY
(2022)
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)
Article
Medicine, General & Internal
Giorgia Gurioli, Vincenza Conteduca, Nicole Brighi, Emanuela Scarpi, Umberto Basso, Giuseppe Fornarini, Alessandra Mosca, Maurizio Nicodemo, Giuseppe Luigi Banna, Cristian Lolli, Giuseppe Schepisi, Giorgia Ravaglia, Isabella Bondi, Paola Ulivi, Ugo De Giorgi
Summary: This study evaluated the prognostic role of CTC gene expression in cabazitaxel-treated mCRPC patients and its association with plasma AR copy number. The results showed that CTC gene expression was significantly associated with overall survival and disease progression. AR-V7 was identified as an important prognostic biomarker, and patients with AR-V7 positivity had poorer outcomes with lower dose cabazitaxel treatment.
Article
Oncology
V Conteduca, M. Medri, L. Mazzoni, U. De Giorgi, I Stanganelli
Summary: This case series describes four patients with anogenital lichen sclerosus et atrophicus (LSA) lesions developing while receiving immunotherapy for advanced cancer, with all cases being grade 2 and showing improvement after specific treatment.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Jacob E. Berchuck, Sylvan C. Baca, Heather M. McClure, Keegan Korthauer, Harrison K. Tsai, Pier Vitale Nuzzo, Kaitlin M. Kelleher, Monica He, John A. Steinharter, Soumya Zacharia, Sandor Spisak, Ji-Heui Seo, Vincenza Conteduca, Olivier Elemento, Joonghoon Auh, Michael Sigouros, Eva Corey, Michelle S. Hirsch, Mary-Ellen Taplin, Toni K. Choueiri, Mark M. Pomerantz, Himisha Beltran, Matthew L. Freedman
Summary: This study reports a novel tissue-informed epigenetic approach for noninvasive detection of neuroendocrine prostate cancer (NEPC) in men with advanced prostate cancer. The results demonstrate that the method can accurately discriminate between NEPC and CR-PRAD with high sensitivity and specificity.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Vincenza Conteduca, Emanuela Scarpi, Daniel Wetterskog, Nicole Brighi, Fabio Ferroni, Alice Rossi, Alessandro Romanel, Giorgia Gurioli, Sara Bleve, Caterina Gianni, Giuseppe Schepisi, Cristian Lolli, Pietro Cortesi, Federica Matteucci, Domenico Barone, Giovanni Paganelli, Francesca Demichelis, Himisha Beltran, Gerhardt Attard, Ugo De Giorgi
Summary: The study found that elevated ptDNA levels in mCRPC patients treated with abiraterone or enzalutamide may be associated with an increased risk of VTE, suggesting the need for closer monitoring and potentially thromboprophylaxis in these patients.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Vincenza Conteduca, Emanuela Scarpi, Paola Caroli, Cristian Lolli, Giorgia Gurioli, Nicole Brighi, Giulia Poti, Alberto Farolfi, Amelia Altavilla, Giuseppe Schepisi, Federica Matteucci, Giovanni Paganelli, Ugo De Giorgi
Summary: In this study, it was found that ptDNA levels in mCRPC patients were associated with metabolic tumour burden, and when combined with functional imaging, they could better predict treatment outcomes. By integrating clinical, molecular, and imaging characteristics, prognostic scores were generated to predict overall survival and progression-free survival, identifying patient groups with different survival probabilities. This study demonstrated the potential of integrating plasma DNA analysis with functional imaging for improved prognostic risk stratification and treatment selection in mCRPC.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Vincenza Conteduca, Chiara Casadei, Emanuela Scarpi, Nicole Brighi, Giuseppe Schepisi, Cristian Lolli, Giorgia Gurioli, Ilaria Toma, Giulia Poti, Alberto Farolfi, Ugo De Giorgi
Summary: This study investigates the correlation between PSA response endpoints, plasma DNA analysis and progression free/overall survival in prostate cancer, highlighting the importance of a multimodal approach in predicting outcomes.
Review
Oncology
Giuseppe Bronte, Vincenza Conteduca, Matteo Landriscina, Antonio Domenico Procopio
Summary: This meta-analysis demonstrates that high levels of circulating MDSCs are associated with worse overall survival in prostate cancer patients, supporting the importance of MDSC detection and targeting in this population.
PROSTATE CANCER AND PROSTATIC DISEASES
(2023)
Article
Oncology
Domenico D'Arca, Leda Severi, Stefania Ferrari, Luca Dozza, Gaetano Marverti, Fulvio Magni, Clizia Chinello, Lisa Pagani, Lorenzo Tagliazucchi, Marco Villani, Gianluca d'Addese, Isabella Piga, Vincenza Conteduca, Lorena Rossi, Giorgia Gurioli, Ugo De Giorgi, Lorena Losi, Maria Paola Costi
Summary: In this study, mass spectrometry and molecular pathway analysis were used to analyze serum samples from patients with ovarian serous carcinoma before the second cycle of FOLFOX-4 therapy. A total of 291 shared expressed proteins were identified, and 12 proteins were found to be significantly associated with treatment response and sample collection time. Network enrichment analysis revealed that these proteins were related to drug-resistant ovarian cancer at the molecular level. This study suggests a new direction for the discovery of protein biomarkers for predicting treatment response.
Article
Oncology
Bhavneet Bhinder, Alison Ferguson, Michael Sigouros, Manik Uppal, Ahmed G. Elsaeed, Rohan Bareja, Hussein Alnajar, Kenneth Wha Eng, Vincenza Conteduca, Andrea Sboner, Juan Miguel Mosquera, Olivier Elemento, Himisha Beltran
Summary: This study analyzed the RNA-sequencing and whole-exome sequencing data of 170 patients with neuroendocrine prostate cancer (NEPC). It found that NEPC has a unique tumor immune landscape compared to other prostate cancer types and small-cell lung cancer (SCLC). NEPC is characterized by a relatively immune-depleted tumor immune microenvironment and less mutations, but has comparable expression of checkpoint genes PD-L1 and CTLA-4 with SCLC. These findings can inform the development of immunotherapy strategies for NEPC.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Guido Giordano, Raffaele Ivan Cincione, Francesca Losavio, Tiziano Senia, Arianna Aquilini Mummolo, Mario Pacilli, Vincenzo Lizzi, Giuseppina Bruno, Annamaria Piscazzi, Vincenza Conteduca, Matteo Landriscina
Summary: Patients with pancreatic cancer often suffer from malnutrition and significant weight loss, which negatively affect treatment outcomes. This study found that nutritional support and pancreatic enzyme replacement therapy can improve overall survival and nutritional parameters in patients with metastatic pancreatic cancer. Early and well-conducted nutritional support can positively impact survival and quality of life.
Article
Biochemistry & Molecular Biology
Maria Concetta Cursano, Emilio Francesco Giunta, Emanuela Scarpi, Chiara Casadei, Alessandra Virga, Paola Ulivi, Sara Bleve, Nicole Brighi, Giorgia Ravaglia, Francesco Pantano, Vincenza Conteduca, Daniele Santini, Ugo De Giorgi
Summary: This study evaluated the prevalence of DNA damage repair (DDR) gene mutations in castration-resistant prostate cancer (CRPC) patients and their impact on clinical outcomes related to bone metastases. The results showed that DDR mutations were associated with larger bone metastases volume, but did not affect skeletal-related events incidence and time to onset.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Giuseppe Luigi Banna, Umberto Basso, Emilio Francesco Giunta, Lucia Fratino, Sara Elena Rebuzzi, Sebastiano Buti, Marco Maruzzo, Ugo De Giorgi, Veronica Murianni, Marika Cinausero, Helga Lipari, Teresa Gamba, Orazio Caffo, Davide Bimbatti, Arianna Dri, Alessandra Mosca, Paola Ermacora, Francesca Vignani, Aichi Msaki, Barbara Bonifacio, Valentina Lombardo, Vincenza Conteduca, Giuseppe Fornarini, Pasquale Rescigno
Summary: This study investigated prognostic factors for older patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving androgen receptor pathway inhibitors (ARPIs) treatment. It found that G8 assessment score <= 14 and PSA decline >= 50% were independent factors associated with worse radiographic progression-free survival and overall survival.
