Review
Oncology
Alessandro Comandone, Federica Vana, Tiziana Comandone, Marcello Tucci
Summary: In recent years, research on the biological mechanisms and treatment of clear cell renal carcinoma has made significant progress. Neo-angiogenesis has been identified as a key player in tumor growth and metastasis, leading to the approval of antiangiogenic drugs with impressive results in treatment outcomes.
Article
Biochemistry & Molecular Biology
Eva Juengel, Pascal Schnalke, Jochen Rutz, Sebastian Maxeiner, Felix K. -H. Chun, Roman A. Blaheta
Summary: Axitinib significantly suppressed the growth of sunitinib-resistant HUVECs and induced cell cycle arrest at the G0/G1 phase. Both axitinib and sorafenib reduced HUVEC tube length and prevented wound closure in sunitinib-resistant HUVECs after six weeks of treatment, with sorafenib showing slightly better results.
Article
Oncology
Zoe Guillaume, Emeline Colomba, Jonathan Thouvenin, Carolina Saldana, Luca Campedel, Clement Dumont, Brigitte Laguerre, Denis Maillet, Cecile Vicier, Frederic Rolland, Delphine Borchiellini, Philippe Barthelemy, Laurence Albiges, Edouard Auclin, Matthieu Roulleaux Dugage, Stephane Oudard, Constance Thibault
Summary: Collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are rare subtypes of kidney cancer with poor prognosis in the metastatic setting. Treatments after first-line chemotherapy showed very low antitumor activity in mCDC/RMC, highlighting the urgent need for a better understanding of the biology of these rare tumors.
Article
Oncology
Juan Jin, Fen Chen, Wenfang He, Li Zhao, Bo Lin, Danna Zheng, Li Chen, Hongchao He, Qiang He
Summary: Aberrant upregulation of SATB2 is associated with poor prognosis in renal cell carcinoma. Inhibition of SATB2 suppresses tumor growth and self-renewal capacities. SATB2 coordinates with NRF2 and SWI/SNF complex to enhance transcriptional activity and DNA accessibility.
Review
Biochemistry & Molecular Biology
Javier Torres-Jimenez, Victor Albarran-Fernandez, Javier Pozas, Maria San Roman-Gil, Jorge Esteban-Villarrubia, Alfredo Carrato, Adriana Rosero, Enrique Grande, Teresa Alonso-Gordoa, Javier Molina-Cerrillo
Summary: Urothelial carcinoma, one of the most prevalent types of cancer worldwide, is experiencing a paradigm shift in its therapeutic landscape with the development of different therapies. Increased knowledge of the pathogenesis and genetic alterations in urothelial carcinoma is also contributing to this transformation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Federica Cosso, Giandomenico Roviello, Gabriella Nesi, Sonia Shabani, Pietro Spatafora, Donata Villari, Martina Catalano
Summary: Renal cell carcinoma (RCC) is the third most common genitourinary cancer and has significant mortality rates. Adjuvant therapy has been explored, but the results for both tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs) have been conflicting. Biomarker identification and subgroup analyses are needed to determine which patients can benefit from adjuvant therapy. This review discusses the rationale for adjuvant treatment in RCC and summarizes the current trials and future directions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Darawan Rinchai, Elena Verzoni, Veronica Huber, Agata Cova, Paola Squarcina, Loris De Cecco, Filippo Braud, Raffaele Ratta, Matteo Dugo, Luca Lalli, Viviana Vallacchi, Monica Rodolfo, Jessica Roelands, Chiara Castelli, Damien Chaussabel, Giuseppe Procopio, Davide Bedognetti, Licia Rivoltini
Summary: This study investigated the immunomodulatory effect of the antiangiogenic agent pazopanib in mRCC patients, showing significant changes in blood immune cell subsets and enhancement in PD-1 expressing cytotoxic T and Natural Killer effectors. This immunomodulation was marked but transient, peaking at the third month of treatment, suggesting the use of antiangiogenics as a preconditioning strategy to improve the efficacy of ICB.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Review
Oncology
Stephanie. A. A. Berg, Bradley. A. A. McGregor
Summary: This article discusses the treatment options and methods for clear cell renal cell carcinoma after radical nephrectomy. Currently, oral vascular endothelial growth factor receptor tyrosine kinase inhibitors or intravenous immune checkpoint inhibitors are the approved treatments, although they can cause toxic reactions. Multiple clinical trials are currently underway to explore the role of adjuvant treatment after nephrectomy, and biomarkers may help determine the effectiveness of treatments for patients.
Article
Chemistry, Medicinal
Sung Min Cho, Yonghyo Kim, Yooju Jung, Minjeong Ko, Gyorgy Marko-Varga, Ho Jeong Kwon
Summary: A novel natural small molecule, voacangine (Voa), has been discovered as a potent antiangiogenic compound that directly binds to and inhibits the kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2). Synthetic molecules based on Voa's chemical structure, such as Voa analogue 19 (V19), show increased antiangiogenic potency without cytotoxic effects and induce significant tumor cell death in a mouse xenograft model. This VEGFR2 modulator, inspired by the natural compound Voa's rigid scaffold, presents a promising candidate for development of new antiangiogenic agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cardiac & Cardiovascular Systems
Kyuwan Lee, Lanie Lindenfeld, Meagan Echevarria, JoAnn Hsu, F. Lennie Wong, Hari K. Narayan, Clayton Lau, LiYing Cai, Sumanta K. Pal, Saro H. Armenian, June-Wha Rhee
Summary: This study evaluated the cardiac function of patients with metastatic renal cell carcinoma (mRCC) receiving treatment with tyrosine kinase inhibitors (TKIs). The results suggest that this treatment strategy is well tolerated in terms of cardiac function.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2023)
Review
Oncology
Hana Studentova, Martina Spisarova, Andrea Kopova, Anezka Zemankova, Bohuslav Melichar, Vladimir Student
Summary: Cytoreductive nephrectomy has long been considered the standard of care for patients with metastatic renal cell carcinoma. However, with the rapid changes in systemic therapy, the importance of this procedure has been widely discussed and disputed. Currently, there is a lack of prospective data on cytoreductive nephrectomy in the immunotherapy era, and retrospective studies with small patient numbers are the main source of evidence. Nevertheless, an individualized approach can help identify patients who may benefit from surgery combined with systemic treatment.
Review
Gastroenterology & Hepatology
Lorenza Rimassa, Richard S. Finn, Bruno Sangro
Summary: Single-agent immune checkpoint inhibitors (ICIs) have limited efficacy in advanced hepatocellular carcinoma (HCC) patients, and approximately 30% of patients show intrinsic resistance to ICIs. Therefore, researchers are exploring combination therapies, such as anti-angiogenic agents and other ICIs. Some trials have shown promising results and potential for clinical application. However, there are still many unanswered questions that require further research.
JOURNAL OF HEPATOLOGY
(2023)
Article
Oncology
Tarini Prasad Sahoo, Chirag Desai, Shyam Agarwal, Amit Rauthan, Boman Dhabhar, Ghanshyam Biswas, Sandeep Batra, Rajat Saha, Arun Philip, Vijay Agarwal, Palanki Satya Dattatreya, P. N. Mohapatra, Chetan Deshmukh, Sagar Bhagat, Saiprasad Patil, Hanmant Barkate
Summary: In advanced Renal Cell Carcinoma (aRCC), systemic therapy with TKIs and IOs is recommended, as surgery has little role in these patients. The sequencing of therapies is crucial in determining subsequent line therapy. However, in India, there are barriers to RCC treatment, including the high cost of immunotherapy and the consideration of disease burden in treatment decision-making. The lack of India-specific guidelines for ccRCC treatment and sequencing further complicates management. This consensus article provides valuable expert recommendations based on clinical evidence for specialists treating advanced ccRCC.
Review
Biochemistry & Molecular Biology
Dariusz Rozkiewicz, Justyna Magdalena Hermanowicz, Iwona Kwiatkowska, Anna Krupa, Dariusz Pawlak
Summary: There has been increasing interest in Bruton's tyrosine kinase (BTK) and its inhibitors in recent decades. BTK is a mediator of the B-cell receptor signaling pathway and has an impact on B-cell proliferation and differentiation. Studies have shown that BTK inhibitors, such as ibrutinib, have potential in treating various cancers and autoimmune diseases. This review article summarizes the latest findings on BTK and its inhibitors, focusing on their clinical applications in cancer and chronic inflammatory diseases.
Review
Pharmacology & Pharmacy
Martina Catalano, Giuseppe Procopio, Pierangela Sepe, Matteo Santoni, Francesco Sessa, Donata Villari, Gabriella Nesi, Giandomenico Roviello
Summary: In the past decade, the management of metastatic renal cell carcinoma (RCC) has greatly improved with frontline immunotherapy, particularly the combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). While this combination is considered the preferred treatment for all metastatic RCC patients, concerns have been raised regarding its efficacy in patients with favorable risk scores. This review aims to explain the rationale behind TKI and ICI combination therapies, summarize the current approved first-line combinations for metastatic RCC, and discuss the challenges and future directions in this field.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Oncology
Anand Sharma, Amish Lakhani, Subhadip Ghosh-Ray, Salma Alam, Anwar Padhani, Andrew Gogbashian, Paul Nathan
Summary: This study aims to evaluate the incidence of small bowel lipomatosis in patients with aRCC on treatment with pazopanib and compare it with other TKIs. The findings show that small bowel lipomatosis is only seen in patients receiving pazopanib and it has no relation with treatment response.
ANTICANCER RESEARCH
(2023)
Article
Medicine, Research & Experimental
Sophie Merrick, Matthew Nankivell, Matteo Quartagno, Caroline S. Clarke, Nalinie Joharatnam-Hogan, Tom Waddell, Brent O'Carrigan, Michael Seckl, Ehsan Ghorani, Emma Banks, Kim Edmonds, George Bray, Rose Woodward, Rachel Bennett, Jonathan Badrock, Will Hudson, Ruth E. Langley, Naveen Vasudev, Lisa Pickering, Duncan C. Gilbert
Summary: The REFINE trial aims to reduce individual patient exposure to immune checkpoint inhibitors (ICI) by extending the dose interval while maintaining efficacy. The trial is investigating different treatment intervals for patients who have responded to conventional doses of ICI. The outcomes of the trial include progression-free survival, overall survival, quality of life, treatment-related toxicity, and cost-effectiveness.
CONTEMPORARY CLINICAL TRIALS
(2023)
Letter
Oncology
Mary Y. Wu, Scott T. C. Shepherd, Annika Fendler, Edward J. Carr, Lewis Au, Ruth Harvey, Giulia Dowgier, Agnieszka Hobbs, Lou S. Herman, Martina Ragno, Lorin Adams, Andreas M. Schmitt, Zayd Tippu, Benjamin Shum, Sheima Farag, Aljosja Rogiers, Nicola O'Reilly, Philip Bawumia, Callie Smith, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Stephanie Hepworth, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Daqi Deng, Bryan Williams, Michael Brown, Simon Caidan, Mike Gavrielides, James I. MacRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O'Flaherty, Sanjay Popat, Nadia Yousaf, Shaman Jhanji, Kate Tatham, David Cunningham, Nicholas Van As, Kate Young, Andrew J. S. Furness, Lisa Pickering, Rupert Beale, Charles Swanton, Sonia Gandhi, Steve Gamblin, David L. V. Bauer, George Kassiotis, Michael Howell, Susanna Walker, Emma Nicholson, James Larkin, Emma C. Wall, Samra Turajlic
Article
Oncology
Drew W. W. Rasco, Theresa Medina, Pippa Corrie, Anna C. C. Pavlick, Mark R. R. Middleton, Paul Lorigan, Chris Hebert, Ruth Plummer, James Larkin, Sanjiv S. S. Agarwala, Adil I. I. Daud, Jiaheng Qiu, Viviana Bozon, Michelle Kneissl, Elly Barry, Anthony J. J. Olszanski
Summary: This study investigated the safety and antitumor activity of tovorafenib, a drug for treating solid tumors, and found that it has good antitumor activity in BRAF-mutated melanoma, particularly in patients who have not received RAF and MEK inhibitors. The study evaluated the safety and pharmacokinetic characteristics of two dosing schedules and identified the recommended dose as 200 mg or 600 mg administered once every other day or once weekly.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2023)
Article
Oncology
Naveen S. Vasudev, Ghislaine Scelo, Kate I. Glennon, Michelle Wilson, Louis Letourneau, Robert Eveleigh, Nazanin Nourbehesht, Madeleine Arseneault, Antoine Paccard, Lars Egevad, Juris Viksna, Edgars Celms, Sharon M. Jackson, Behnoush Abedi-Ardekani, Anne Y. Warren, Peter J. Selby, Sebastian Trainor, Michael Kimuli, Jon Cartledge, Naeem Soomro, Adebanji Adeyoju, Poulam M. Patel, Magdalena B. Wozniak, Ivana Holcatova, Antonin Brisuda, Vladimir Janout, Estelle Chanudet, David Zaridze, Anush Moukeria, Oxana Shangina, Lenka Foretova, Marie Navratilova, Dana Mates, Viorel Jinga, Ljiljana Bogdanovic, Bozidar Kovacevic, Anne Cambon-Thomsen, Guillaume Bourque, Alvis Brazma, Jorg Tost, Paul Brennan, Mark Lathrop, Yasser Riazalhosseini, Rosamonde E. Banks
Summary: Targeted gene sequencing can help in risk prediction and adjuvant treatment decisions for patients with resected localized ccRCC. Mutations in the VHL gene have a significant impact on patient outcomes, independent of other gene mutations. Genomic characterization can personalize treatment discussions and inform future adjuvant trial design.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
James Larkin, Michele Del Vecchio, Mario Mandala, Helen Gogas, Ana M. Arance Fernandez, Stephane Dalle, Charles Lance Cowey, Michael Schenker, Jean -Jacques Grob, Vanna Chiarion-Sileni, Ivan Marquez-Rodas, Marcus O. Butler, Anna Maria Di Giacomo, Mark R. Middleton, Jose Lutzky, Luis de la Cruz-Merino, Petr Arenberger, Victoria Atkinson, Andrew G. Hill, Leslie A. Fecher, Michael Millward, Paul D. Nathan, Nikhil I. Khushalani, Paola Queirolo, Corey Ritchings, Maurice Lobo, Margarita Askelson, Hao Tang, Sonia Dolfi, Paolo A. Ascierto, Jeffrey Weber
Summary: The study demonstrates that adjuvant nivolumab significantly improves recurrence-free survival and distant metastasis-free survival in high-risk melanoma patients who have undergone surgical resection, with sustained long-term benefits. Biomarkers such as tumor mutational burden, tumor PD-L1, intratumoral CD8+ T cells and IFNy-associated gene expression signature are associated with improved treatment outcomes, but their predictive value is limited.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Reinhard Dummer, Pippa Corrie, Ralf Gutzmer, Tarek M. Meniawy, Michele Del Vecchio, Celeste Lebbe, Michele Guida, Caroline Dutriaux, Brigitte Dreno, Nicolas Meyer, Pier Francesco Ferrucci, Stephane Dalle, Muhammad Adnan Khattak, Jean-Jacques Grob, Karen Briscoe, James Larkin, Sandrine Mansard, Thierry Lesimple, Massimo Guidoboni, Silvia Sabatini, Erika Richtig, Rudolf Herbst, Maurice Lobo, Margarita Askelson, Paolo A. Ascierto, Michele Maio
Summary: The study aimed to evaluate the safety and efficacy of nivolumab plus ipilimumab followed by nivolumab monotherapy in patients with advanced melanoma. It found that the treatment was tolerable and had similar efficacy in all treated population with various subgroups, but reduced efficacy in patients with specific characteristics, indicating a need for novel treatment options.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Paolo Antonio Ascierto, Evan J. Lipson, Reinhard Dummer, James Larkin, Georgina V. Long, Rachel E. Sanborn, Vanna Chiarion-Sileni, Brigitte Dreno, Stephane Dalle, Dirk Schadendorf, Margaret K. Callahan, Marta Nyakas, Victoria Atkinson, Carlos Alberto Gomez-Roca, Naoya Yamazaki, Hussein A. Tawbi, Naomey Sarkis, Deepti Warad, Sonia Dolfi, Priyam Mitra, Satyendra Suryawanshi, Jean-Jacques Grob
Summary: Preliminary research shows that nivolumab and relatlimab have better efficacy in treating advanced melanoma patients who have previously received anti-PD-(L)1 treatment. The RELATIVITY-047 trial demonstrated that nivolumab and relatlimab, compared to nivolumab alone, significantly improved progression-free survival in previously untreated advanced melanoma patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Caroline Robert, Matteo S. Carlino, Catriona Mcneil, Antoni Ribas, Jean-Jacques Grob, Jacob Schachter, Marta Nyakas, Damien Kee, Teresa M. Petrella, Arnold Blaustein, Michal Lotem, Ana Arance, Adil I. Daud, Omid Hamid, James Larkin, James Anderson, Clemens Krepler, Dmitri Grebennik, Georgina V. Long
Summary: Clinical trials often have multiple end points that mature at different times. Clinical Trial Updates provide a platform to publish additional results from studies where the primary end point has already been reported. This article presents the 7-year follow-up and efficacy results of pembrolizumab in advanced melanoma patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Janet E. Brown, Kara-Louise Royle, Walter Gregory, Christy Ralph, Anthony Maraveyas, Omar Din, Timothy Eisen, Paul Nathan, Tom Powles, Richard Griffiths, Robert Jones, Naveen Vasudev, Matthew Wheater, Abdel Hamid, Tom Waddell, Rhona McMenemin, Poulam Patel, James Larkin, Guy Faust, Adam Martin, Jayne Swain, Janine Bestall, Christopher McCabe, David Meads, Vicky Goh, Tze Min Wah, Julia Brown, Jenny Hewison, Peter Selby, Fiona Collinson
Summary: This study aimed to compare the non-inferiority of a tyrosine kinase inhibitor drug-free interval strategy with a conventional continuation strategy in the first-line treatment of advanced clear cell renal cell carcinoma. The results showed that non-inferiority between the two groups could not be concluded in terms of overall survival and quality-adjusted life-years (QALYs). However, treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma.
Article
Oncology
Ketty Peris, Maria Concetta Fargnoli, Roland Kaufmann, Petr Arenberger, Lars Bastholt, Nicole Basset Seguin, Veronique Bataille, Lieve Brochez, Veronique del Marmol, Reinhard Dummer, Ana-Marie Forsea, Caroline Gaudy-Marqueste, Catherine A. Harwood, Axel Hauschild, Christoph Hoeller, Lidija Kandolf, Nicole W. J. Kellerners-Smeets, Aimilios Lallas, Ulrike Leiter, Josep Malvehy, Branka Marinovic, Zeljko Mijuskovic, David Moreno-Ramirez, Eduardo Nagore, Paul Nathan, Alexander J. Stratigos, Eggert Stockfleth, Luca Tagliaferri, Myrto Trakatelli, Ricardo Vieira, Iris Zalaudek, Claus Garbe, EADO, EDF, ESTRO, UEMS, V EAD
Summary: Basal cell carcinoma is the most common malignant tumor in white populations. This article provides updated recommendations on the diagnosis and treatment of BCC, including classification, surgical treatment, topical therapies, and the use of hedgehog inhibitors and immunotherapy. Regular skin examinations and long-term follow-up are also recommended for high-risk patients.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Simona Manacorda, Maria De Toro Carmena, Ciara Malone, Ha Mo Linh Le, Andrew J. S. Furness, James Larkin, Andreas M. Schmitt
Summary: This study investigated the efficacy of PD-1-directed antibody-based therapy in patients with symptomatic melanoma brain metastases (MBM) and concurrent treatment with corticosteroids. The findings showed that patients only derived modest benefit from the treatment, but those with disease response had the potential to derive long-term benefit, justifying the use of this therapy in this group in the absence of other more effective treatment options.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Adi Diab, Helen Gogas, Shahneen Sandhu, Georgina V. Long, Paolo A. Ascierto, James Larkin, Mario Sznol, Fabio Franke, Tudor E. Ciuleanu, Caio Pereira, Eva Munoz Couselo, Fernanda Bronzon Damian, Michael Schenker, Aldo Perfetti, Celeste Lebbe, Gaelle Quereux, Friedegund Meier, Brendan D. Curti, Carlos Rojas, Yull Arriaga, Haisu Yang, Ming Zhou, Shruthi Ravimohan, Paul Statkevich, Mary A. Tagliaferri, Nikhil I. Khushalani
Summary: Despite the efficacy of Bempegaldesleukin (BEMPEG) in the treatment of melanoma, the PIVOT IO 001 study did not meet its primary end points, with increased toxicity observed with the combination of BEMPEG plus NIVO.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Sarah Howlett, Thomas J. Carter, Heather M. Shaw, Paul D. Nathan
Summary: Tebentafusp is a novel immunotherapy agent that targets specific cells and has shown efficacy in treating advanced solid cancer and uveal melanoma. It is the first bispecific T-cell engager to demonstrate overall survival benefit and offers new possibilities for the management of advanced UM.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2023)