Article
Medicine, General & Internal
J. H. Strickler, H. Satake, T. J. George, R. Yaeger, A. Hollebecque, I Garrido-Laguna, M. Schuler, T. F. Burns, A. L. Coveler, G. S. Falchook, M. Vincent, Y. Sunakawa, L. Dahan, D. Bajor, S-Y Rha, C. Lemech, D. Juric, M. Rehn, G. Ngarmchamnanrith, P. Jafarinasabian, Q. Tran, D. S. Hong
Summary: This study evaluated the safety and efficacy of sotorasib in patients with KRAS p.G12C-mutated pancreatic cancer who had previously received treatment. The results showed that sotorasib demonstrated anticancer activity and had an acceptable safety profile in these patients.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Oncology
Sahar F. Bannoura, Husain Yar Khan, Asfar S. Azmi
Summary: KRAS mutations are common in cancer, and recent advancements have shown that small molecule inhibitors can be developed against KRAS G12C, although there is still no agent to target KRAS G12D. However, significant progress has been made in developing compounds that can bind to and inhibit KRAS G12D, including MRTX1133. Additionally, an immunotherapeutic approach using adoptive T-cell transfer has shown promise in targeting G12D in pancreatic cancer.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Cian O'Leary, Grace Murphy, Yong Yeung, Ming Tang, Vikram Jain, Connor G. O'Leary
Summary: Non-small-cell lung cancer (NSCLC) is a common and often fatal malignancy, with Kirsten rat sarcoma virus (KRAS) mutation being a commonly mutated oncogene in NSCLC. Recently developed KRAS G12C inhibitors have overcome the therapeutic hurdle of targeting KRAS mutations. While these medications show substantial response rates in heavily pre-treated NSCLC patients, phase-3 evidence has not yet demonstrated an overall survival benefit compared to standard-of-care chemotherapy. Additionally, these medications may have a negative interaction with immunotherapies, leading to higher hepatotoxicity rates. Despite these limitations, these medications represent an important advancement in targeted and personalized oncological treatment, and future trials may provide further meaningful outcomes for guiding treatment in this patient cohort.
Article
Medicine, General & Internal
Rona Yaeger, Jared Weiss, Meredith S. Pelster, Alexander Spira, Minal Barve, Sai-Hong Ou, Ticiana A. Leal, Tanios S. Bekaii-Saab, Cloud P. Paweletz, Grace A. Heavey, James G. Christensen, Karen Velastegui, Thian Kheoh, Hirak Der-Torossian, Samuel J. Klempner
Summary: In this study, the researchers investigated the clinical efficacy of adagrasib in combination with cetuximab for heavily pretreated patients with metastatic colorectal cancer harboring mutant KRAS G12C. The results showed that the overall response rate was 19% in the adagrasib monotherapy group, with a median progression-free survival of 5.6 months, and 46% in the combination therapy group, with a median progression-free survival of 6.9 months. Both groups experienced reversible adverse events.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Oncology
Tony Kiat Hon Lim, Ferdinandos Skoulidis, Keith M. Kerr, Myung-Ju Ahn, Joshua R. Kapp, Fernando A. Soares, Yasushi Yatabe
Summary: KRAS is the most commonly mutated oncogene in advanced NSCLC, and the approval of KRAS G12C-selective inhibitors has made it a druggable target. Real-world evidence shows geographic differences in KRAS G12C prevalence, and co-mutations with other genes are also common. Testing and reporting of KRAS G12C should be included in routine biomarker testing before first-line therapy.
Review
Pharmacology & Pharmacy
Natalie Mausey, Zachery Halford
Summary: This article evaluates the safety and efficacy of KRAS-targeting agents, sotorasib and adagrasib, in treating KRAS G12C-mutated non-small cell lung cancer (NSCLC). It highlights their promising outcomes and the need for further research to optimize their therapeutic application in this high-risk population.
ANNALS OF PHARMACOTHERAPY
(2023)
Article
Oncology
Takamasa Koga, Kenichi Suda, Toshio Fujino, Shuta Ohara, Akira Hamada, Masaya Nishino, Masato Chiba, Masaki Shimoji, Toshiki Takemoto, Takeo Arita, Michael Gmachl, Marco H. Hofmann, Junichi Soh, Tetsuya Mitsudomi
Summary: The study developed in vitro models of KRAS G12C cancer resistant to sotorasib and adagrasib, and found that most clones harbored secondary KRAS mutations which showed differential sensitivity to the inhibitors. Sequential use of sotorasib and adagrasib may be considered in some cases, while a combination of BI-3406 and trametinib could be an effective strategy to overcome resistance caused by secondary Y96D and Y96S mutations.
JOURNAL OF THORACIC ONCOLOGY
(2021)
Review
Oncology
Mariacarmela Santarpia, Giuliana Ciappina, Calogera Claudia Spagnolo, Andrea Squeri, Maria Ilenia Passalacqua, Andres Aguilar, Maria Gonzalez-Cao, Elisa Giovannetti, Nicola Silvestris, Rafael Rosell
Summary: Selective KRAS G12C inhibitors have shown significant clinical benefit in pretreated NSCLC patients with KRAS G12C mutation, improving the therapeutic scenario for this molecularly-defined subgroup.
TRANSLATIONAL LUNG CANCER RESEARCH
(2023)
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)
Review
Oncology
Misako Nagasaka, Bindu Potugari, Alexis Nguyen, Ammar Sukari, Asfar S. Azmi, Sai-Hong Ignatius Ou
Summary: KRAS, a common proto-oncogene with mutations in various malignancies, lacks effective targeted therapy leading to poor prognosis. While a KRAS G12C inhibitor has been approved for a subset of patients, resistance remains a challenge and alternative treatment strategies are being explored, including combination therapy, direct inhibition, and gene editing techniques.
CANCER TREATMENT REVIEWS
(2021)
Article
Biotechnology & Applied Microbiology
Francesco Palma, Alessandra Affinito, Silvia Nuzzo, Giuseppina Roscigno, Iolanda Scognamiglio, Francesco Ingenito, Lola Martinez, Monica Franzese, Mario Zanfardino, Andrea Soricelli, Alfonso Fiorelli, Gerolama Condorelli, Cristina Quintavalle
Summary: miR-34c-3p is a potential novel biomarker for positive prognosis in KRAS-mutated NSCLC patients, showing increased apoptosis and decreased proliferation in cells, and potentially targeting CDK1 for therapeutic purposes.
CANCER GENE THERAPY
(2021)
Article
Oncology
Angelina S. Bortoletto, Ronald J. Parchem
Summary: Extensive studies have shown that misregulation of individual miRNAs is associated with cancer. Recently, it has been discovered that mutations in the miRNA biogenesis and processing machinery are also involved in several malignancies. These mutations can cause global miRNA misregulation and contribute to cancer development. Additionally, it has been found that mutant KRAS can affect the activity of miRNA regulatory pathway members, further promoting tumorigenesis. Targeting both mutant KRAS and the miRNA core machinery may present a potential strategy for cancer treatment.
Article
Oncology
Gabriela Palma, Faisal Khurshid, Kevin Lu, Brian Woodward, Hatim Husain
Summary: Patients with tumors harboring KRAS G12C mutations have poor prognosis, but targeted therapies like sotorasib and Adagrasib have shown promising overall response rates. While single agent efficacy is observed, combination approaches may offer better outcomes.
NPJ PRECISION ONCOLOGY
(2021)
Review
Oncology
Matthew Z. Guo, Kristen A. Marrone, Alexander Spira, Samuel Rosner
Summary: Adagrasib is a newly approved targeted therapy for KRAS(G12C)-mutated non-small-cell lung cancer. It has shown clinical efficacy with an objective response rate of 42.9% and a median duration of response of 8.5 months in pretreated patients. Gastrointestinal adverse events were the most common, occurring in 97.4% of patients, with grade 3+ events in 44.8% of patients. This review provides comprehensive data on the preclinical and clinical use of adagrasib, as well as guidelines for clinical administration and toxicity management. It also discusses resistance mechanisms, other KRAS(G12C) inhibitors in development, and future directions for adagrasib-based combination therapies.
Review
Chemistry, Medicinal
Claudia Korzeniecki, Ronny Priefer
Summary: KRAS genes are commonly mutated in cancer, and targeting KRAS mutant cancers has proven difficult due to lack of success with direct inhibitors. Researchers are now focusing on targeting other areas of the MAPK signaling pathway to inhibit KRAS function.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Editorial Material
Gastroenterology & Hepatology
Camillo Porta, Chiara Broglia, Francesca Negri
Article
Oncology
Fotios Loupakis, Rossana Intini, Chiara Cremolini, Armando Orlandi, Andrea Sartore-Bianchi, Filippo Pietrantonio, Nicoletta Pella, Andrea Spallanzani, Emanuela Dell'Aquila, Mario Scartozzi, Emmanuele De Luca, Lorenza Rimassa, Vincenzo Formica, Francesco Leone, Lorenzo Calvetti, Giuseppe Aprile, Lorenzo Antonuzzo, Federica Urbano, Hans Prenen, Francesca Negri, Samantha Di Donato, Pasquale Buonandi, Gianluca Tomasello, Antonio Avallone, Fable Zustovich, Roberto Moretto, Carlotta Antoniotti, Lisa Salvatore, Maria Alessandra Calegari, Salvatore Siena, Federica Morano, Elena Ongaro, Stefano Cascinu, Daniele Santini, Pina Ziranu, Marta Schirripa, Federica Buggin, Alessandra Anna Prete, Ilaria Depetris, Paola Biason, Sara Lonardi, Vittorina Zagonel, Matteo Fassan, Massimo Di Maio
EUROPEAN JOURNAL OF CANCER
(2019)
Article
Oncology
Francesca Negri, Cecilia Bozzetti, Giuseppe Pedrazzi, Cinzia Azzoni, Lorena Bottarelli, Anna Squadrilli, Costanza Lagrasta, Ione Tamagnini, Alessandra Bisagni, Moira Ragazzi, Rosa Porzio, Gianluca Tomasello, Daniele Mori, Francesco Leonardi, Letizia Gnetti, Pellegrino Crafa, Roberto Sala, Stefano Cascinu
Article
Oncology
Vincenzo Catalano, Francesca Bergamo, Chiara Cremolini, Bruno Vincenzi, Francesca Negri, Paolo Giordani, Paolo Alessandroni, Rossana Intini, Silvia Stragliotto, Daniele Rossini, Beatrice Borelli, Daniele Santini, Donatella Sarti, Marco B. L. Rocchi, Sara Lonardi, Alfredo Falcone, Vittorina Zagonel, Rodolfo Mattioli, Francesco Graziano
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2020)
Article
Oncology
Francesca Mazzoni, Paolo Petreni, Enrico Vasile, Michele Panebianco, Andrea Casadei-Gardini, Francesca Negri, Alice Lunghi, Serena Pillozzi, Caterina Vivaldi, Erika Gervasi, Giovanni Luca Frassineti, Luca Messerini, Genny Jocolle, Alessandra Bisagni, Lorenzo Antonuzzo, Giulio Rossi
Review
Biochemistry & Molecular Biology
Luigi Laghi, Francesca Negri, Federica Gaiani, Tommaso Cavalleri, Fabio Grizzi, Gian Luigi de'Angelis, Alberto Malesci
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Oncology
Stefano Cascinu, Rossana Berardi, Roberto Bianco, Domenico Bilancia, Alberto Zaniboni, Daris Ferrari, Stefania Mosconi, Andrea Spallanzani, Luigi Cavanna, Silvana Leo, Francesca Negri, Giordano D. Beretta, Alberto Sobrero, Maria Banzi, Alberto Morabito, Alessandro Bittoni, Roberta Marciano, Domenica Ferrara, Silvia Noventa, Maria C. Piccirillo, Roberto Labianca, Cristina Mosconi, Andrea Casadei Gardini, Ciro Gallo, Francesco Perrone
Summary: The combination chemotherapy regimen of Nab-paclitaxel and Gemcitabine showed superior efficacy compared to Gemcitabine alone in patients with unresectable locally advanced pancreatic cancer, reducing disease progression rate and distant relapses, and improving progression-free survival. This randomized trial provides evidence supporting the use of combination chemotherapy in this setting.
EUROPEAN JOURNAL OF CANCER
(2021)
Review
Biochemistry & Molecular Biology
Federica Gaiani, Federica Marchesi, Francesca Negri, Luana Greco, Alberto Malesci, Gian Luigi de'Angelis, Luigi Laghi
Summary: The review delves into molecular genetics, molecular phenotypes, and the tumor micro-environment in the pathogenesis of colorectal cancer, as well as the impact of gut homeostasis and micronutrients on disease progression. It also touches upon the role of gut microbiota in CRC, and the challenges and promises of pharmacological interventions in restraining disease progression at different stages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Francesca Negri, Letizia Gnetti, Giuseppe Pedrazzi, Enrico Maria Silini, Camillo Porta
Summary: This study found that elevated AFP plasma levels before sorafenib therapy were associated with inferior survival, suggesting a possible role of AFP in resistance to sorafenib therapy. The study also revealed no correlation between AFP level and VEGFR2 expression on cancer cells.
Article
Oncology
Francesca Negri, Gabriele Missale, Anna Degli Antoni, Camillo Porta
Summary: In the HAART era, HCC is becoming a common late complication of HIV infection, with the complex interaction of HIV and hepatitis playing a key role in morbidity and mortality. Limited data on sorafenib effectiveness and safety in HIV-infected patients suggest comparable outcomes to HIV-uninfected patients in selected subgroups. Additionally, data on other systemic treatments like tyrosine kinase inhibitors and ICIs are scarce, but may offer promising options for HCC patients with HIV infection.
TRANSLATIONAL ONCOLOGY
(2021)
Editorial Material
Oncology
Francesca Negri, Camillo Porta
Letter
Oncology
Francesca Negri, Carlo Aschele
JOURNAL OF CLINICAL ONCOLOGY
(2022)
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)
Article
Multidisciplinary Sciences
Francesca Negri, Annamaria De Giorgi, Annalisa Gilli, Cinzia Azzoni, Lorena Bottarelli, Letizia Gnetti, Matteo Goldoni, Laura Manotti, Paolo Sgargi, Maria Michiara, Francesco Leonardi, Guido Rindi, Stefano Cascinu, Enrico Maria Silini
SCIENTIFIC REPORTS
(2019)