Review
Medicine, General & Internal
Marc-Oliver Grimm, Katharina Leucht, Susan Foller
Summary: Systemic therapy for metastatic renal cell carcinoma has evolved over the past two decades, with significant improvements in survival and quality of life seen in advanced patients. Treatment options have shifted towards combination therapies with PD(L)-1 immune checkpoint inhibitors, as well as VEGFR-TKI/ICI combinations. Risk stratification using IMDC criteria and detailed patient counseling on treatment efficacy and potential side effects are crucial in individual treatment decisions.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Urology & Nephrology
Maria I. Carlo, Kyrollis Attalla, Yousef Mazaheri, Sounak Gupta, Onur Yildirim, Samuel J. Murray, Devyn T. Coskey, Ritesh Kotecha, Chung-Han Lee, Darren R. Feldman, Paul Russo, Sujata Patil, Robert J. Motzer, Jonathan A. Coleman, Jeremy C. Durack, Ying-Bei Chen, Oguz Akin, A. Ari Hakimi, Martin H. Voss
Summary: This study evaluated the outcomes of localized kidney cancer patients who received immunotherapy prior to surgery. It found that this approach was safe and feasible, without significant surgical delays and with an expected rate of immune-related adverse events.
Article
Pharmacology & Pharmacy
SiNi Li, JianHe Li, LiuBao Peng, YaMin Li, XiaoMin Wan
Summary: The study found that in untreated advanced renal cell carcinoma patients, nivolumab-plus-cabozantinib is the most effective treatment strategy, while sunitinib is the least costly option. Pembrolizumab-plus-axitinib, nivolumab-plus-cabozantinib, and sunitinib are considered cost-effective alternatives.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Lauren J. Brown, Ines Pires da Silva, Tania Moujaber, Bo Gao, Rina Hui, Howard Gurney, Matteo Carlino, Adnan Nagrial
Summary: Immunotherapy has shown significant benefits in improving overall survival in patients with advanced solid organ malignancies. Factors associated with better 5-year survival include ECOG score of 0 and occurrence of irAEs, while presence of bone metastases and liver metastases are associated with worse 5-year survival. These results support the long-term benefits of immunotherapy and highlight the impact of metastatic site and cancer type on survival.
Review
Biotechnology & Applied Microbiology
Stefano Bibbo, Serena Porcari, Livio Enrico Del Vecchio, Andrea Severino, Benjamin H. Mullish, Gianluca Ianiro, Antonio Gasbarrini, Giovanni Cammarota
Summary: The gut microbiome plays a crucial role in cancer development and treatment. Modulating the gut microbiome has shown to enhance the response to immune checkpoint inhibitors, especially in the treatment of renal cancer.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2023)
Article
Oncology
Patrick Demkowicz, Renelle Pointdujour-Lim, Sofia Miguez, Yesung Lee, Bailey S. C. L. Jones, Christopher A. Barker, Marcus Bosenberg, David H. Abramson, Alexander N. Shoushtari, Harriet Kluger, Jasmine H. Francis, Mario Sznol, Mathieu F. Bakhoum
Summary: This study retrospectively analyzed clinical data of patients with metastatic uveal melanoma and found that female sex, treatment with immune checkpoint inhibitors, and the absence of liver metastasis were associated with better survival outcomes. These findings highlight the potential of immunotherapy in treating metastatic uveal melanoma.
Article
Biochemistry & Molecular Biology
Takuro Kobayashi, Masayoshi Nagata, Yoshihiro Ikehata, Yuki Nagashima, Naoya Nagaya, Yan Lu, Shigeo Horie
Summary: We have found that the clonality of TCR repertoire is associated with the development of irAEs in RCC patients treated with ICIs. The proportion of specific sequences within the TCR repertoire is higher in patients with more severe irAEs.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Review
Oncology
Claire Masson, Jonathan Thouvenin, Philippe Boudier, Denis Maillet, Sabine Kuchler-Bopp, Philippe Barthelemy, Thierry Massfelder
Summary: Immunotherapy-based combinations have become the standard of care for metastatic clear cell renal cell carcinoma (mccRCC) patients. However, a significant percentage of patients do not respond to these therapies or develop acquired resistance. The lack of validated biomarkers hinders the adaptation of treatment strategies.
Article
Health Care Sciences & Services
Duong H. T. Vo, Gerard McGleave, Ian M. Overton
Summary: The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine. However, many patients are unresponsive to ICI therapy. This study used the IMMUNETS gene coregulation networks to investigate the response to nivolumab in advanced melanoma patients and identified potential prognostic biomarkers.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Joao Calmeiro, Mylene A. Carrascal, Adriana Ramos Tavares, Daniel Alexandre Ferreira, Celia Gomes, Maria Teresa Cruz, Amilcar Falcao, Bruno Miguel Neves
Summary: Immunotherapy has led to a paradigm shift in the treatment of malignancies, especially through the combination of multiple immunotherapeutic strategies for superior clinical outcomes.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Oncology
I. Resch, A. Bruchbacher, J. Franke, H. Fajkovic, M. Remzi, S. F. Shariat, M. Schmidinger
Summary: The study evaluated the benefit of immune checkpoint inhibitors (ICIs) in metastatic renal cell carcinoma patients across different treatment lines. Results showed that ICIs or ICI combinations are active in all treatment lines and should be offered to heavily pretreated patients. Patient selection based on tumor and patient factors allows for maximal benefit from ICI-based therapies.
Article
Cell Biology
Yumeng Zhang, Premsai Kumar, Jacob J. Adashek, William P. Skelton, Jiannong Li, Aram Vosoughi, Jad Chahoud, Brandon J. Manley, Philippe E. Spiess
Summary: Modulating the COX-2 pathway has not shown improved outcomes in metastatic renal cell carcinoma patients undergoing immune checkpoint inhibitor therapies. However, concurrent use of NSAIDs was associated with worse progression and survival outcomes.
Article
Oncology
Ryan C. Augustin, Sarah Newman, Aofei Li, Marion Joy, Maureen Lyons, Mary P. Pham, Peter Lucas, Katelyn Smith, Cindy Sander, Brian Isett, Diwakar Davar, Yana G. Najjar, Hassane M. Zarour, John M. Kirkwood, Jason John Luke, Riyue Bao
Summary: In this study, we characterized acral melanoma (AM) and investigated its response to immune checkpoint inhibitors (ICIs). We found differential gene expression and pathway activation in a non-T cell-inflamed tumor microenvironment (TME) of AM, which may contribute to its poor response to ICIs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Viktoria Stuhler, Lisa Herrmann, Steffen Rausch, Arnulf Stenzl, Jens Bedke
Summary: This study evaluated the predictive and prognostic value of the systemic immune-inflammation index (SII) in patients with metastatic renal cell carcinoma (mRCC) treated with first-line ipilimumab plus nivolumab. High SII score was associated with worse progression-free survival and overall survival, while a low SII index was associated with higher clinical benefit rate. An increase in SII after 12 weeks of therapy was significantly associated with tumor progression at first imaging. SII could be used to refine decision making in patients treated with ipilimumab plus nivolumab.
Article
Oncology
Tony Z. Zhuang, Deepak Ravindranathan, Yuan Liu, Dylan J. Martini, Jacqueline T. Brown, Bassel Nazha, Greta Russler, Lauren B. Yantorni, Sarah Caulfield, Bradley C. Carthon, Omer Kucuk, Viraj A. Master, Mehmet Asim Bilen
Summary: This study reports on the role of the neutrophil-to-eosinophil ratio as a potential biomarker in metastatic renal cell carcinoma, suggesting that elevated baseline NER may be associated with worse clinical outcomes.
Article
Radiology, Nuclear Medicine & Medical Imaging
Aloyse Fourquet, Adrian Rosenberg, Esther Mena, Joanna J. Shih, Baris Turkbey, Maxime Blain, Ethan Bergvall, Frank Lin, Stephen Adler, Ilhan Lim, Ravi A. Madan, Fatima Karzai, James L. Gulley, William L. Dahut, Bradford J. Wood, Richard Chang, Elliot Levy, Peter L. Choyke, Liza Lindenberg
Summary: This study compared the use of different PET tracers (F-18-DCFPyL, F-18-NaF, and F-18-FDG) in men with metastatic prostate cancer. The results showed that F-18-DCFPyL was the most effective in detecting metastatic lesions, while F-18-NaF was better at detecting bone metastases. The study also found that there were differences in the detection rates of the same lesion using different tracers.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Oncology
Borys Hrinczenko, Nicholas Iannotti, Sanjay Goel, David Spigel, Howard Safran, Matthew H. Taylor, Jaafar Bennouna, Deborah J. Wong, Karen Kelly, Claire Verschraegen, Marcis Bajars, Juliane Manitz, Mary Ruisi, James L. Gulley
Summary: This study found that approximately 11% of patients with advanced non-small-cell lung cancer received 2 years or more of avelumab treatment in a large trial, and experienced prolonged response or continued clinical benefit.
Editorial Material
Biochemistry & Molecular Biology
Nicholas P. Tschernia, Scott M. Norberg, James L. Gulley
Article
Oncology
Keith T. Schmidt, Fatima Karzai, Marijo Bilusic, Lisa M. Cordes, Cindy H. Chau, Cody J. Peer, Susan Wroblewski, Alwin D. R. Huitema, Jan H. M. Schellens, James L. Gulley, William L. Dahut, William D. Figg, Ravi A. Madan
Summary: This article reports the results of a trial evaluating the efficacy of NLG207 in combination with enzalutamide for patients with metastatic castration-resistant prostate cancer who had previously progressed on enzalutamide. The study found that the combination treatment was not well tolerated in patients, leading to the termination of the study.
Article
Oncology
Cristina Mullenix, Madison Ballman, Haobin Chen, Shannon Swift, Meredith J. McAdams, Yo-Ting Tsai, Renee N. Donahue, Trina Poretta, Sarthak Gupta, Patrick J. Loehrer, Jeffrey Schlom, James L. Gulley, Arun Rajan
Summary: ICIs have revolutionized cancer treatment, but immune-mediated toxicity is a concern for TETs patients. The cases presented in this report highlight the spectrum of immune-mediated musculoskeletal adverse events in TETs patients.
Article
Oncology
Arun Rajan, Jhanelle E. Gray, Siddhartha Devarakonda, Ruemu Birhiray, Borys Korchin, Erika Menius, Renee N. Donahue, Jeffrey Schlom, James L. Gulley
Summary: CV301 in combination with PD-1 inhibitors is safe and clinically active in advanced NSCLC patients, without an increased frequency or severity of immune-related adverse events.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Mary Helen Barcellos-Hoff, James L. Gulley
Summary: Despite the increasing number of TGFI3 inhibitors tested in cancer patients, there has been no clinical benefit achieved yet. The main obstacle to effective TGFI3 inhibition is the diverse mechanisms by which TGFI3 promotes tumor growth. TGFI3 is involved in regulating DNA repair and immune suppression, which can be used to synergize genotoxic therapy and immunotherapy for the benefit of cancer patients.
CLINICAL CANCER RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Cody J. Peer, Keith T. Schmidt, Oluwatobi Arisa, William J. Richardson, Koosha Paydary, Daniel A. Goldstein, James L. Gulley, William D. Figg, Mark J. Ratain
Summary: Atezolizumab, a humanized monoclonal antibody against PD-L1, was approved in 2016. Standard dose regimens result in high plasma concentrations, indicating the need for alternative dosing strategies to reduce exposure burden.
JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Oncology
Alexander Spira, Michael S. Wertheim, Edward J. Kim, Benjamin Tan, Heinz-Josef Lenz, Petros Nikolinakos, Patricia L. Rich, Genevieve Jehl, Andreas Machl, Rena Ito, James L. Gulley, Scott Kopetz
Summary: A phase I study on bintrafusp alfa in heavily pretreated patients with colorectal cancer showed promising early signs of clinical efficacy and manageable safety profile.
Article
Oncology
Margaret E. Gatti-Mays, Nicholas P. Tschernia, Julius Strauss, Ravi A. Madan, Fatima H. Karzai, Marijo Bilusic, Jason Redman, Houssein Abdul Sater, Charalampos S. Floudas, Nicole J. Toney, Renee N. Donahue, Caroline Jochems, Jennifer L. Marte, Deneise Francis, Sheri McMahon, Elizabeth Lamping, Lisa Cordes, Jeffrey Schlom, James L. Gulley
Summary: The results of this study showed that biweekly NHS-IL12 treatment was safe for patients with advanced cancers. NHS-IL12 is a first-in-class fusion protein used in this trial. Patients received NHS-IL12 every two weeks, and the results demonstrated stable disease status for the patients.
Article
Oncology
Emerson A. Lim, Michael T. Schweizer, Kim N. Chi, Rahul Aggarwal, Neeraj Agarwal, James Gulley, Edward Attiyeh, James Greger, Shujian Wu, Pharavee Jaiprasart, John Loffredo, Nibedita Bandyopadhyay, Hong Xie, Aaron R. Hansen
Summary: PSMA expression is maintained in all stages of prostate cancer. In a phase 1 study, a bispecific antibody targeting PSMA-expressing tumor cells and CD3-expressing T cells showed manageable cytokine release syndrome and temporary decline in PSA in patients with metastatic castration-resistant prostate cancer. Treatment-related deaths and radiographic responses were not observed. PSMA is a potential therapeutic target for T-cell redirection in prostate cancer.
CLINICAL GENITOURINARY CANCER
(2023)
Article
Oncology
Michael B. Atkins, Paolo A. Ascierto, David Feltquate, James L. Gulley, Douglas B. Johnson, Nikhil Khushalani, Jeffrey Sosman, Timonthy A. Yap, Harriet Kluger, Ryan J. Sullivan, Hussein Tawbi
Summary: Immunotherapy alone does not work for all tumors, so combining it with signal transduction inhibitors, such as antiangiogenic therapies, can enhance its effectiveness. Combination therapies with immunotherapy have shown improved antitumor activity in various solid tumor settings and have received regulatory approval for the treatment of several types of cancer. However, many patients still experience progression after combination treatment, highlighting the need for new strategies to address resistance to immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Ryan Chang, James L. Gulley, Lawrence Fong
Summary: Immunotherapies, such as immune checkpoint inhibitors and cellular therapies, have revolutionized cancer treatment, but the development of successful cancer vaccines remains challenging. Only two vaccines have shown improved survival in advanced disease: sipuleucel-T and talimogene laherparepvec, which target specific antigens and utilize tumors in situ to prime responses. In this review, we examine the challenges and opportunities in developing therapeutic cancer vaccines.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Sungwon Lee, Daniel C. Elton, James L. Gulley, Perry J. Pickhardt, William L. Dahut, Ravi A. Madan, Peter A. Pinto, Deborah E. Citrin, Ronald M. Summers
Summary: Traditionally, coronary artery calcium scoring is used to evaluate atherosclerotic risk factors for cardiovascular disease and cancer. However, this study found that atherosclerotic plaque in the aortoiliac region is not associated with prostate cancer. On the other hand, the presence of abdominal plaques is closely correlated with age and Framingham risk scores.
Article
Biochemical Research Methods
Joshua A. Welsh, Bryce Killingsworth, Julia Kepley, Tim Traynor, Sean Cook, Jason Savage, Jenn Marte, Min-Jung Lee, Hoyoung M. Maeng, Michelle L. Pleet, Setty Magana, Andre Gorgens, Cecile L. Maire, Katrin Lamszus, Franz L. Ricklefs, Maria J. Merino, W. Marston Linehan, Tim Greten, Tomer Cooks, Curtis C. Harris, Andrea Apolo, Asim Abdel-Mageed, Alexander R. Ivanov, Jane B. Trepel, Matthew Roth, Mercedes Tkach, Aleksandar Milosavljevic, Clotilde Thery, Amy LeBlanc, Jay A. Berzofsky, Eytan Ruppin, Kenneth Aldape, Kevin Camphausen, James L. Gulley, Ionita Ghiran, Steve Jacobson, Jennifer C. Jones
Summary: Extracellular vesicles (EVs) carry various types of proteins and nucleic acids, and can provide a retrospective snapshot of cell state through liquid biopsies. Multiplex assays for high-parameter EV protein detection are still being developed. To facilitate EV repertoire studies, we developed MPAPASS software for stitched multiplex analysis, EV database-compatible reporting, and visualization of EV repertoires.
CELL REPORTS METHODS
(2022)
