Article
Oncology
Rona Yaeger, Riccardo Mezzadra, Jenna Sinopoli, Yu Bian, Michelangelo Marasco, Esther Kaplun, Yijun Gao, HuiYong Zhao, Arnaud Da Cruz Paula, Yingjie Zhu, Almudena Chaves Perez, Kalyani Chadalavada, Edison Tse, Sudhir Chowdhry, Sydney Bowker, Qing Chang, Besnik Qeriqi, Britta Weigelt, Gouri J. Nanjangud, Michael F. Berger, Hirak Der-Torossian, Kenna Anderes, Nicholas D. Socci, Jinru Shia, Yonina R. Murciano-Goroff, Bob Li, James G. Christensen, Jorge S. Reis-Filho, David B. Solit, Elisa de Stanchina, Scott W. Lowe, Neal Rosen, Sandra Misale
Summary: Combining KRASG12C and EGFR inhibitors is an effective treatment for colorectal cancer. However, secondary resistance can reduce its efficacy. Our study found that resistance alterations preventing inhibition of ERK signaling are detected at a low frequency, except for KRASG12C amplification, which increases over time. Upon drug withdrawal, resistant cells undergo senescence, but mTOR signaling remains elevated. Targeting the senescence response may be a potential therapeutic vulnerability to overcome acquired resistance.
Article
Biochemistry & Molecular Biology
Juanjuan Feng, Zhongwei Hu, Xinting Xia, Xiaogu Liu, Zhengke Lian, Hui Wang, Liren Wang, Cun Wang, Xueli Zhang, Xiufeng Pang
Summary: MIT researchers have found a correlation between KRAS(G12D) mutation and CRC, and through experiments they have proven that the effectiveness of the KRAS(G12D) inhibitor MRTX1133 treatment is related to EGFR inhibition, indicating that a combination of these two drugs may have clinical significance for patients with KRAS(G12D)-mutated CRC.
Review
Biochemistry & Molecular Biology
Alessandro Caputo, Angela D'Ardia, Francesco Sabbatino, Caterina Picariello, Chiara Ciaparrone, Pio Zeppa, Antonio D'Antonio
Summary: The standard of care for advanced non-small-cell lung cancer involves detecting actionable mutations, with the Idylla EGFR test being able to detect 51 mutations in 2.5 hours. Cytological material can be used for this test, but caution should be taken as the accuracy may be reduced when using scraped stained smears as input.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Chih-Jie Shen, Ren-Hao Chan, Bo-Wen Lin, Nien-Chi Li, Ying-Hsuan Huang, Wen-Chang Chang, Ben-Kuen Chen
Summary: This study found that IL-8 and the activation of KRAS affect ROS production and metastasis in hyperlipidemia-associated CRC, providing potentially new treatment options for this type of CRC.
Article
Oncology
Roberto Chalela, Jose Gregorio Gonzalez-Garcia, Karys Khilzi, Victor Curull, Albert Sanchez-Font, Raquel Longaron, Maria Teresa Rodrigo-Calvo, Clara Martin-Ontiyuelo, Joaquim Gea, Beatriz Bellosillo
Summary: Driver mutations in non-tumoral lung cells were detected in a proportion of subjects with ADC, indicating their potential role in carcinogenesis. The presence of these mutations in the absence of coexisting mutations in the primary tumor was confirmed through highly sensitive PCR methods.
PATHOLOGY & ONCOLOGY RESEARCH
(2021)
Article
Medicine, Research & Experimental
Linlin Yang, Zhefeng Li, Daniel W. Binzel, Peixuan Guo, Terence M. Williams
Summary: This study suggests that nanoparticles targeting mutant KRAS can effectively suppress cancer cell proliferation and migration, and enhance sensitivity to chemoradiotherapy in lung cancer. These findings highlight the potential of this nanoparticle-based platform as a novel treatment strategy for KRAS-driven human cancers.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Oncology
Luiz Henrique Araujo, Bianca Mendes Souza, Laura Rabelo Leite, Sabrina A. F. Parma, Natalia P. Lopes, Frederico S. V. Malta, Maira C. M. Freire
Summary: KRAS G12C mutation frequency is higher than other driver mutations in colorectal and non-small cell lung cancer, suggesting KRAS testing should be considered for all patients regardless of clinical or demographic characteristics.
Article
Biochemistry & Molecular Biology
Nguyen Quoc Khanh Le, Quang Hien Kha, Van Hiep Nguyen, Yung-Chieh Chen, Sho-Jen Cheng, Cheng-Yu Chen
Summary: The study introduced a machine learning model for selecting and predicting EGFR and KRAS mutations in NSCLC patients using a minimal number of semantic radiomics features, with the genetic algorithm plus XGBoost classifier showing the best accuracy in detecting these mutations. This noninvasive machine learning-based model demonstrated robust prediction of EGFR and KRAS mutations in patients with NSCLC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Shafia Rahman, Shimon Garrel, Michael Gerber, Radhashree Maitra, Sanjay Goel
Summary: Colorectal cancer is a common cancer in the United States, and approximately 45% of patients with metastatic colorectal cancer have KRAS mutations, requiring a more personalized treatment approach for these patients.
Article
Biochemistry & Molecular Biology
Luca Jaromi, Veronika Csongei, Monika Vesel, ElHusseiny Mohamed Mahmud Abdelwahab, Amina Soltani, Zsofia Torok, Gabor Smuk, Veronika Sarosi, Judit Erzsebet Pongracz
Summary: This study found that KRAS and EGFR driver mutations have differential effects on drug transporter expression and cisplatin-induced WNT signaling microenvironment in lung adenocarcinoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Wei Chong, Xingyu Zhu, Huicheng Ren, Chunshui Ye, Kang Xu, Zhe Wang, Shengtao Jia, Liang Shang, Leping Li, Hao Chen
Summary: This study elucidates the molecular heterogeneity of KRAS-mutant CRC and reveals new biological subtypes and therapeutic possibilities for these tumors.
Article
Biochemistry & Molecular Biology
Jiuna Zhang, Xiaoyu Jiang, Jie Yin, Shiying Dou, Xiaoli Xie, Ting Liu, Yijun Wang, Shuling Wang, Xue Zhou, Dongxuan Zhang, Huiqing Jiang
Summary: RNF141 plays an oncogenic role in colorectal cancer by upregulating KRAS activity, which promotes tumor growth, cell proliferation, migration, and apoptosis by interacting with KRAS to induce its activation and enrichment on the plasma membrane.
Review
Oncology
Chongkai Wang, Marwan Fakih
Summary: Recent research has shown promising antitumor activity of highly potent KRAS(G12C) specific inhibitors in patients with NSCLC and colorectal cancer. Despite encouraging progress, further efforts are needed to identify biomarkers predicting response to KRAS(G12C) inhibition and develop strategies to overcome resistance.
CURRENT ONCOLOGY REPORTS
(2021)
Article
Oncology
Daniel J. Becker, Kyung M. Lee, Steve Y. Lee, Kristine E. Lynch, Danil Makarov, Scott E. Sherman, Christy D. Morrissey, Michael J. Kelley, Julie A. Lynch
Summary: This study evaluated the clinical use of KRAS testing and EGFR mAb treatment in colorectal cancer patients in the Veterans Affairs Healthcare System. The results showed underuse of KRAS testing, especially among older patients and those treated at lower-volume CRC centers, as well as high rates of potentially guideline discordant underuse of EGFR mAb in patients with KRAS-WT tumors. Efforts to understand barriers to precision oncology are needed to maximize patient benefit.
JCO PRECISION ONCOLOGY
(2021)
Article
Medicine, General & Internal
Marwan G. Fakih, Lisa Salvatore, Taito Esaki, Dominik P. Modest, David P. Lopez-Bravo, Julien Taieb, Michalis V. Karamouzis, Erika Ruiz-Garcia, Tae-Won Kim, Yasutoshi Kuboki, Fausto Meriggi, David Cunningham, Kun-Huei Yeh, Emily Chan, Joseph Chao, Yaneth Saportas, Qui Tran, Chiara Cremolini, Filippo Pietrantonio
Summary: In this study, the combination of KRAS G12C inhibitor sotorasib and EGFR inhibitor panitumumab showed longer progression-free survival compared to standard treatment in patients with chemorefractory metastatic colorectal cancer.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Monia Sisi, Michele Fusaroli, Andrea De Giglio, Francesco Facchinetti, Andrea Ardizzoni, Emanuel Raschi, Francesco Gelsomino
Summary: This study conducted a real-world pharmacovigilance analysis on psychiatric adverse events (AEs) associated with marketed ALK inhibitors in patients with advanced NSCLC. The results showed a higher proportion of psychiatric AEs with lorlatinib compared to other ALK TKIs, suggesting a potential class effect of psychiatric reactions for ALK TKIs.
Article
Oncology
Gianluca Taronna, Alessandro Leonetti, Filippo Gustavo Dall'Olio, Alessandro Rizzo, Claudia Parisi, Sebastiano Buti, Paola Bordi, Stefano Brocchi, Rita Golfieri, Andrea Ardizzoni, Nicola Sverzellati, Marcello Tiseo
Summary: Transient asymptomatic pulmonary opacities (TAPO), a benign finding observed in patients treated with osimertinib, are radiologically characterized by focal ground-glass opacity. No specific clinical variables were associated with the onset of TAPO, and there was no significant difference in clinical outcomes between TAPO-positive and TAPO-negative groups.
Review
Oncology
Francesca Comito, Rachele Pagani, Giada Grilli, Francesca Sperandi, Andrea Ardizzoni, Barbara Melotti
Summary: This review summarizes the current research areas for the treatment of metastatic or unresectable advanced cutaneous melanoma, including immune checkpoint inhibitors, cell therapy, vaccines, targeted therapy, and combination strategies. While preliminary efficacy data from early phase trials are available in some areas, confirmation in larger patient cohorts is needed. Understanding the biological effects of the molecules and identifying predictive biomarkers remain crucial for selecting patient populations most likely to benefit from novel emerging treatment strategies.
Article
Oncology
Elisa Andrini, Giuseppe Lamberti, Francesca Mazzoni, Ferdinando Riccardi, Andrea Bonetti, Alessandro Follador, Fabrizio Artioli, Carlo Genova, Fausto Barbieri, Antonio Frassoldati, Matteo Brighenti, Ida Colantonio, Giulia Pasello, Corrado Ficorella, Saverio Cinieri, Marcello Tiseo, Francesco Gelsomino, Michele Tognetto, Karim Rihawi, Andrea Ardizzoni
Summary: Extended-stage small-cell lung cancer (ES-SCLC) is an aggressive subtype with poor prognosis. The combination of chemotherapy, antiangiogenic therapy, and immunotherapy may improve survival. The CeLEBrATE trial aims to assess the efficacy and safety of this combination treatment.
Article
Oncology
Fabiana Perrone, Giulia Mazzaschi, Roberta Minari, Michela Verze, Cinzia Azzoni, Lorena Bottarelli, Rita Nizzoli, Monica Pluchino, Annalisa Altimari, Elisa Gruppioni, Francesca Sperandi, Elisa Andrini, Giorgia Guaitoli, Federica Bertolini, Fausto Barbieri, Stefania Bettelli, Lucia Longo, Maria Pagano, Candida Bonelli, Elena Tagliavini, Davide Nicoli, Alessandro Ubiali, Adriano Zangrandi, Serena Trubini, Manuela Proietto, Letizia Gnetti, Marcello Tiseo
Summary: This study provides insights into the clinical characteristics, treatment response, and survival outcomes of BRAF mutant non-small cell lung cancer, focusing on the differences between V600E and non-V600E populations. The results suggest that V600E mutation may be associated with longer progression-free survival, and factors such as ECOG PS, age, and bone metastasis impact overall survival and progression-free survival.
Article
Oncology
Giulia Mazzaschi, Fabiana Perrone, Roberta Minari, Michela Verze, Cinzia Azzoni, Lorena Bottarelli, Monica Pluchino, Maria Pia Armillotta, Annalisa Ubaldi, Annalisa Altimari, Elisa Gruppioni, Francesca Sperandi, Elisa Andrini, Giorgia Guaitoli, Stefania Bettelli, Lucia Longo, Federica Bertolini, Fausto Barbieri, Maria Pagano, Candida Bonelli, Elena Tagliavini, Davide Nicoli, Alessandro Ubiali, Adriano Zangrandi, Serena Trubini, Manuela Proietto, Letizia Gnetti, Marcello Tiseo
Summary: The study retrospectively evaluated the clinical impact of KRAS mutations in 297 KRAS-mutant NSCLC patients, finding no significant differences in survival and treatment outcomes based on different KRAS mutations, with chemotherapy-treated patients showing worse prognosis and immunotherapy-based regimens potentially prolonging survival. This research may provide valuable insights for predicting outcomes in KRAS-mutant NSCLC patients.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
Giulia Mazzaschi, Alessandro Olivari, Antonio Pavarani, Costanza Anna Maria Lagrasta, Caterina Frati, Denise Madeddu, Bruno Lorusso, Silvia Dallasta, Chiara Tommasi, Antonino Musolino, Marcello Tiseo, Maria Michiara, Federico Quaini, Pellegrino Crafa
Summary: This study aimed to analyze the clinical outcome of GB patients by integrating molecular, immunophenotypic, and MR imaging features. The results showed that MGMT methylation was associated with prolonged overall survival, and GB patients with high mean ADC at MRI had increased survival. PD-L1 and the overall number of TILs and CD163+ TAMs had a marginal impact on patient outcome, while the density of vascular-associated CD4+ lymphocytes emerged as the most significant prognostic factor. Genetic, MR imaging, and immune descriptors were correlated with overall survival. Combining negative predictors (MGMT unmethylation, low mean ADC, and low V-CD4+ TILs) provided a highly significant risk stratification model in GB patients.
Article
Radiology, Nuclear Medicine & Medical Imaging
Alessandra Guido, Dajana Cuicchi, Paolo Castellucci, Francesco Cellini, Francesca Di Fabio, Fabiola Lorena Rojas Llimpe, Lidia Strigari, Milly Buwenge, Savino Cilla, Francesco Deodato, Gabriella Macchia, Erika Galietta, Rita Golfieri, Andrea Ardizzoni, Rocco Maurizio Zagari, Stefano Fanti, Gilberto Poggioli, Lorenzo Fuccio, Alessio G. Morganti
Summary: This study aimed to evaluate the pathological complete response rate of locally advanced rectal cancer after high-dose neoadjuvant chemoradiation based on FDG-PET/CT. The results showed that dose escalation on the target in the final phase of chemoradiation is well tolerated and can provide a high pathological complete response rate.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Oncology
Emanuel Raschi, Michele Fusaroli, Valentina Giunchi, Andrea Repaci, Carla Pelusi, Veronica Mollica, Francesco Massari, Andrea Ardizzoni, Elisabetta Poluzzi, Uberto Pagotto, Guido Di Dalmazi
Summary: This study described the clinical features of adrenal insufficiency caused by anticancer drugs targeting vascular endothelial growth factor receptor. A strong signal was found for multi-targeted tyrosine kinase inhibitors, especially in combination with immunotherapy. These findings highlight the importance of timely pharmacovigilance in detecting and characterizing adverse events, supporting patient care.
Article
Oncology
Jordi Remon, Guillermo Villacampa, Francesco Facchinetti, Massimo Di Maio, Florit Marcuse, Marcello Tiseo, Monique Hochstenbag, Lizza E. L. Hendriks, Benjamin Besse
Summary: There is no standard second-line treatment for patients with advanced TET after platinum-based chemotherapy. Although ICB is a potential treatment strategy, its efficacy seems limited with an increased risk of ir-AEs, thus hampering its application in daily clinical practice.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Andrea Ardizzoni, Sergio Azevedo, Belen Rubio-Viqueira, Delvys Rodriguez-Abreu, Jorge Alatorre-Alexander, Hans J. M. Smit, Jinming Yu, Konstantinos Syrigos, Elen Hoglander, Monika Kaul, Jonathan Tolson, Youyou Hu, Hans Kristian Vollan, Thomas Newsom-Davis
Summary: Atezolizumab therapy improves survival in previously treated NSCLC patients and is associated with manageable safety. The TAIL study showed that Atezolizumab has a similar risk-benefit profile in diverse patient populations, which can guide treatment decisions for patients generally excluded from pivotal clinical trials.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Fabiana Perrone, Elda Favari, Giuseppe Maglietta, Michela Verze, Monica Pluchino, Roberta Minari, Roberto Sabato, Giulia Mazzaschi, Annalisa Ronca, Alessandra Rossi, Alessio Cortellini, Federica Pecci, Luca Cantini, Melissa Bersanelli, Federico Quaini, Marcello Tiseo, Sebastiano Buti
Summary: This study aimed to investigate the impact of cholesterol efflux capacity on the clinical outcomes of patients with advanced non-small cell lung cancer and metastatic renal cell carcinoma treated with immune checkpoint inhibitors. The results showed that blood cholesterol levels and serum transporters were associated with patients' overall survival, progression-free survival, and clinical benefit. Passive diffusion demonstrated positive prognostic value in terms of these clinical outcomes.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Francesca Negri, Lorena Bottarelli, Giuseppe Pedrazzi, Michele Maddalo, Ludovica Leo, Gianluca Milanese, Roberto Sala, Michele Lecchini, Nicoletta Campanini, Cecilia Bozzetti, Andrea Zavani, Gianluca Di Rienzo, Cinzia Azzoni, Enrico Maria Silini, Nicola Sverzellati, Federica Gaiani, Gian Luigi De' Angelis, Letizia Gnetti
Summary: This study investigated the expression of NICD and its ligands and the role of radiomics in selecting treatment-naive metastatic CRC patients receiving bevacizumab. The results showed that high NICD and Jag1 expression are associated with progressive disease and early disease progression to anti VEGF-based therapy. Radiomic analysis integrated with quantitative information, clinical, and histological data showed the highest performance in predicting the outcome of CRC patients.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Cesare Gridelli, Marcello Tiseo, Diego Luigi Cortinovis, Maria Rita Migliorino, Vito Barbieri, Paolo Bironzo, Alessandra Bearz, Ilaria Attili, Filippo de Marinis
Summary: ALK tyrosine kinase inhibitors have significantly improved the treatment of NSCLC patients with ALK rearrangements. In Italy, Alectinib and brigatinib are the preferred first-line treatments, with lorlatinib pending approval. Age and performance status have little impact on treatment choice, but treatment compliance and toxicity profile should be considered. The treatment selection should take into account the patient's comorbidities and polypharmacotherapy interactions.
Meeting Abstract
Oncology
D. Ross Camidge, Hye Ryun Kim, Myung-Ju Ahn, James Chih-Hsin Yang, Ji-Youn Han, Maximilian Hochmair, Ki Hyeong Lee, Angelo Delmonte, Rosario Garcia Campelo, Dong-Wan Kim, Frank Griesinger, Enriqueta Felip, Raffaele Califano, Alexander I. Spira, Michael Thomas, Scott N. Gettinger, Marcello Tiseo, Yuyin Liu, Pingkuan Zhang, Sanjay Popat
JOURNAL OF CLINICAL ONCOLOGY
(2022)
