Article
Oncology
Marina Marinkovic, Lennart J. Pors, Vincent van den Berg, Femke P. Peters, Ann Schalenbourg, Leonidas Zografos, Alessia Pica, Jan Hrbacek, Sjoerd G. Van Duinen, T. H. Khanh Vu, Jaco C. Bleeker, Coen R. N. Rasch, Martine J. Jager, Gregorius P. M. Luyten, Nanda Horeweg
Summary: This study demonstrates that proton therapy abroad for uveal melanoma is effective in controlling tumors and preserving eyes, with 94% of patients showing controlled tumors and 81% preserving their eyes after five years. However, around 30% of patients experienced cancer spread beyond the eye, leading to blindness or severe visual impairment in 79% of patients after proton therapy. Factors such as tumor size, localization, and proton therapy dose are important for the risk of decline in visual acuity.
Article
Oncology
Ernesto Rossi, Michela Croce, Francesco Reggiani, Giovanni Schinzari, Marianna Ambrosio, Rosaria Gangemi, Giampaolo Tortora, Ulrich Pfeffer, Adriana Amaro
Summary: Survival rates for metastatic uveal melanoma have not significantly improved over the years, as it differs from cutaneous melanoma and is resistant to current therapies. The main obstacles are the activation of oncogenic signaling pathways that cannot be targeted, the lack of tumor specific neo-antigens for immune response, and the pro-tumorigenic microenvironment that promotes tumor progression. However, new drugs targeting oncogenic pathways, innovative immune therapy approaches, and liver-specific treatments offer hope for improving outcomes.
Article
Biochemistry & Molecular Biology
Jiafang Ma, Li Weng, Boris C. Bastian, Xu Chen
Summary: The study identified the CYSLTR2 -> GNAQ/11 -> PLC beta signaling pathway as a key driver of uveal melanoma proliferation, with the PKC/RasGRP3/MAPK signaling branch being essential. Inhibition of the MAPK branch, but not the FAK branch, synergized with inhibition of the proximal cascade, providing a blueprint for combination therapy. All oncogenic signaling could be suppressed by the GNAQ/11 inhibitor YM-254890, highlighting its potential for treating neoplastic disorders with G alpha q pathway mutations.
Article
Multidisciplinary Sciences
Tomas Radivoyevitch, Emily C. Zabor, Arun D. Singh
Summary: The long-term survival of uveal melanoma patients in the US was compared using different methods, finding that death due to melanoma became rare beyond 20 years with normal life expectancy reached at 25 years after primary therapy. Relative survival methods provide more realistic estimates by comparing the survival to that of a normal matched population.
Article
Multidisciplinary Sciences
Grace B. Phelps, Hannah R. Hagen, Adam Amsterdam, Jacqueline A. Lees
Summary: This study investigates the oncogenic signaling events and the role of MITF in uveal melanoma (UM) using zebrafish models. The findings suggest that YAP signaling is the major mediator of UM and MITF acts as a tumor suppressor in UM.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, General & Internal
Paul Nathan, Jessica C. Hassel, Piotr Rutkowski, Jean-Francois Baurain, Marcus O. Butler, Max Schlaak, Ryan J. Sullivan, Sebastian Ochsenreither, Reinhard Dummer, John M. Kirkwood, Anthony M. Joshua, Joseph J. Sacco, Alexander N. Shoushtari, Marlana Orloff, Josep M. Piulats, Mohammed Milhem, April K. S. Salama, Brendan Curti, Lev Demidov, Lauris Gastaud, Cornelia Mauch, Melinda Yushak, Richard D. Carvajal, Omid Hamid, Shaad E. Abdullah, Chris Holland, Howard Goodall, Sophie Piperno-Neumann
Summary: The randomized trial of tebentafusp for metastatic uveal melanoma showed a higher 1-year overall survival rate among patients who received tebentafusp compared to those who received the investigator's choice of therapy, indicating superior efficacy.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Lei Cao, Shuzhen Chen, Rainie Sun, Charles R. R. Ashby Jr, Liuya Wei, Zoufang Huang, Zhe-Sheng Chen
Summary: On May 2, 2022, the FDA granted orphan drug designation to darovasertib, a novel oral inhibitor of PKC, for treating uveal melanoma. Uveal melanoma has a high risk of progression and poor prognosis. The GNAQ and GNA11 gene mutations and activation of PKC and MAPK pathways are crucial in the development of uveal melanoma. Darovasertib is more potent than other PKC inhibitors and shows better tolerability and safety. Clinical trials have demonstrated its synergistic effect with MEK inhibitors in uveal melanoma treatment.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Oncology
Paula Milan-Rois, Anan Quan, Frank J. Slack, Alvaro Somoza
Summary: Uveal melanoma is a rare and deadly cancer that requires novel treatment and diagnostic approaches. Long non-coding RNAs (lncRNAs) are crucial in cancer and other diseases, offering potential as therapeutic targets and diagnostic markers. Understanding lncRNAs related to uveal melanoma could inspire the development of new treatments and diagnostics, with their interaction with other non-coding RNAs playing a significant role in cancer development.
Article
Cell Biology
David Gentien, Elnaz Saberi-Ansari, Nicolas Servant, Ariane Jolly, Pierre de la Grange, Fariba Nemati, Geraldine Liot, Simon Saule, Aurelie Teissandier, Deborah Bourc'his, Elodie Girard, Jennifer Wong, Julien Masliah-Planchon, Erkan Narmanli, Yuanlong Liu, Emma Torun, Rebecca Goulancourt, Manuel Rodrigues, Laure Villoing Gaude, Cecile Reyes, Mateo Bazire, Thomas Chenegros, Emilie Henry, Audrey Rapinat, Mylene Bohec, Sylvain Baulande, Radhia M'kacher, Eric Jeandidier, Andre Nicolas, Giovanni Ciriello, Raphael Margueron, Didier Decaudin, Nathalie Cassoux, Sophie Piperno-Neumann, Marc-Henri Stern, Johan Harmen Gibcus, Job Dekker, Edith Heard, Sergio Roman-Roman, Joshua J. Waterfall
Summary: Through comprehensive multi-omics characterization, we identified genomic instability as a hallmark of uveal melanoma (UM) and confirmed the recurrent deletion in the BAP1 promoter associated with high risk of metastasis in UM patients. We also discovered the upregulation of PRAME as an independent prognostic biomarker and a potential therapeutic target in UM.
Review
Oncology
Dominic Lapadula, Jeffrey L. Benovic
Summary: Uveal melanoma is a deadly eye cancer with no FDA-approved standard of care for metastatic disease. Mutations in the G(q/11) signaling pathway drive the pathogenesis of this cancer. Treatment of the primary tumor is often effective, but a high percentage of patients develop metastasis, most commonly to the liver.
Review
Oncology
Cristina Barbagallo, Michele Stella, Giuseppe Broggi, Andrea Russo, Rosario Caltabiano, Marco Ragusa
Summary: Uveal melanoma (UM) is a rare eye cancer with a high mortality rate due to metastases. UM and cutaneous melanoma (CM) have different molecular alterations and biological behavior. This review discusses the genetic and epigenetic landscapes of UM, with potential implications for biomarker identification and therapeutic targets.
Review
Oncology
Mihail Zemba, Otilia-Maria Dumitrescu, Alina Gabriela Gheorghe, Madalina Radu, Mihai Alexandru Ionescu, Andrei Vatafu, Valentin Dinu
Summary: Radiation therapy is the most commonly used eye-sparing treatment for uveal melanoma worldwide, but it has many complications that can affect vision. Understanding the different adverse effects, risk factors, prognosis, and available treatments for each complication is crucial for guiding treatment choices.
Article
Oncology
Prisca Bustamante, Leo Piquet, Solange Landreville, Julia Burnier
Summary: Uveal melanoma is an intraocular tumor that tends to metastasize to the liver. Despite identifying early driver mutations, the process of UM metastasis remains incompletely understood. A better understanding of genetic, molecular, and environmental factors could lead to new approaches for UM treatment.
SEMINARS IN CANCER BIOLOGY
(2021)
Review
Oncology
Aaron B. Beasley, Fred K. Chen, Timothy W. Isaacs, Elin S. Gray
Summary: Uveal melanoma is the most common primary intraocular malignancy, and despite successful local treatment, the risk of metastatic disease remains. Intraocular tumor biopsy is the current prognostic method, but it is invasive and limited by sampling variability. Liquid biopsy, including circulating tumor cells, circulating tumor DNA, microRNA, and exosomes, holds great potential for minimally invasive genetic characterization of tumors.
BRITISH JOURNAL OF CANCER
(2022)
Editorial Material
Oncology
A. Rodrigues, R. Cosman, A. M. Joshua
Summary: Metastatic uveal melanoma has a poor prognosis and different pathophysiology from cutaneous melanoma, limiting treatment options. Targeted therapy with darovasertib towards protein kinase C is well tolerated and shows early signs of efficacy, indicating the need for further exploration and combination strategies.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Travis E. Grotz, Jennifer A. Yonkus, Cornelius A. Thiels, Susanne G. Warner, Robert R. McWilliams, Amit Mahipal, Tanios S. Bekaii-Saab, Sean P. Cleary, Michael L. Kendrick, Mark J. Truty
Summary: This study evaluated the safety and outcomes of surgical resection in patients with limited peritoneal metastasis (PM) from pancreatic ductal adenocarcinoma (PDAC). The results showed that cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment is safe and feasible for selected patients with low-volume PM, and it has favorable short-term outcomes.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Medicine, General & Internal
Lipika Goyal, Funda Meric-Bernstam, Antoine Hollebecque, Juan W. Valle, Chigusa Morizane, Thomas B. Karasic, Thomas A. Abrams, Junji Furuse, Robin K. Kelley, Philippe A. Cassier, Heinz-Josef Kluempen, Heung-Moon Chang, Li-Tzong Chen, Josep Tabernero, Do-Youn Oh, Amit Mahipal, Markus Moehler, Edith P. Mitchell, Yoshito Komatsu, Kunihiro Masuda, Daniel Ahn, Robert S. Epstein, Abdel-Baset Halim, Yao Fu, Tehseen Salimi, Volker Wacheck, Yaohua He, Mei Liu, Karim A. Benhadji, John A. Bridgewater
Summary: In this study, 103 patients with FGFR2-altered intrahepatic cholangiocarcinoma were treated with futibatinib for a median duration of 17.1 months. The results showed that futibatinib treatment could effectively inhibit tumor growth, improve survival, and maintain quality of life for patients.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Editorial Material
Pharmacology & Pharmacy
Sakti Chakrabarti, Amit Mahipal
Review
Oncology
Amr Mohamed, Sulin Wu, Mohamed Hamid, Amit Mahipal, Sakti Cjakrabarti, David Bajor, J. Eva Selfridge, Sylvia L. L. Asa
Summary: Appendiceal neuroendocrine neoplasms (ANENs) are usually found incidentally during appendectomy. They are rare, accounting for a small percentage of intestinal neoplasms. The management of ANENs varies based on histological differentiation and tumor grade.
Editorial Material
Oncology
Travis E. Grotz, Jennifer A. Yonkus, Cornelius A. Thiels, Susanne G. Warner, Robert McWilliams, Amit Mahipal, Tanios S. Bekaii-Saab, Sean P. Cleary, Michael L. Kendrick, Mark J. Truty
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Sri Harsha Tella, Nathan Foster, Shi Qian, Tran Nguyen, Mitesh J. Borad, Robert R. McWilliams, Steven R. Alberts, Wen Wee Ma, Sakti Chakrabarti, Briant Fruth, Jaclynn Wessling, Mindy Hartgers, Leslie Washburn, Martin E. Fernandez-Zapico, Tara L. Hogenson, Henry Pitot, Zhaohui Jin, Amit Mahipal
Summary: This study investigated the safety and efficacy of trifluridine/tipiracil in combination with irinotecan for refractory, advanced unresectable biliary tract carcinoma. The combination treatment showed promising results in terms of progression-free and overall survival. Adverse events were observed, but the genetic mutation status did not affect treatment response. Larger randomized trials are needed to confirm these findings.
Article
Oncology
Nirosha D. Perera, Tiffany R. Bellomo, Walker M. Schmidt, Henry K. Litt, Margaret Shyu, MaKenna A. Stavins, Max M. Wang, Alexander Bell, Massoud Saleki, Katherine Wolf, Ruxandra Ionescu, Jacqueline J. Tao, Sunjong Ji, Ryan M. O'Keefe, Matthew Pun, Jordan M. Takasugi, Jecca R. Steinberg, Ronald S. Go, Brandon E. Turner, Amit Mahipal
Summary: This study evaluates the representation of female participants in oncology clinical trials in the US, finding that women are underrepresented in surgical and invasive trials, but overrepresented in hematologic and pancreatic trials. Additionally, industry-funded trials have higher female representation compared to government and academic-funded trials.
Article
Oncology
Stephanie Pitts, Amit Mahipal, David Bajor, Amr Mohamed
Summary: Parathyroid hormone-related protein (PTHrP) secretion is often found in solid tumors, but it is rare in neuroendocrine tumors. We presented a case report of a patient with metastatic pancreatic neuroendocrine tumor (PNET) who developed hypercalcemia due to elevated PTHrP. The patient's hypercalcemia and PTHrP levels improved with the use of a long-acting somatostatin analogue. The optimal management of malignant hypercalcemia caused by PTHrP-producing PNETs was also discussed based on current literature.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Shishir K. Maithel, Jessica M. Keilson, Hop S. Tran Cao, Manali Rupji, Amit Mahipal, Bruce S. Lin, Milind M. Javle, Sean P. Cleary, Mehmet Akce, Jeffrey M. Switchenko, Flavio G. Rocha
Summary: The study aimed to evaluate the feasibility of using gemcitabine, cisplatin, and nab-paclitaxel as neoadjuvant treatment in high-risk intrahepatic cholangiocarcinoma patients. The results showed that this neoadjuvant treatment approach was feasible and safe, and did not adversely affect perioperative outcomes.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Shishir K. Maithel, Jessica M. Keilson, Hop S. Tran Cao, Manali Rupji, Amit Mahipal, Bruce S. Lin, Milind M. Javle, Sean P. Cleary, Mehmet Akce, Jeffrey M. Switchenko, Flavio G. Rocha
ANNALS OF SURGICAL ONCOLOGY
(2023)
Letter
Oncology
Sakti Chakrabarti, Amit Mahipal
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Surgery
Mohamedraed Elshami, Lauryn Bailey, Richard S. Hoehn, John B. Ammori, Jeffrey M. Hardacre, J. Eva Selfridge, David Bajor, Amr Mohamed, Sakti Chakrabarti, Amit Mahipal, Jordan M. Winter, Lee M. Ocuin
Summary: This study examined differences in surgical intervention for early-stage hepatocellular carcinoma patients at minority-serving hospitals compared to non-minority-serving hospitals. The findings revealed that patients treated at minority-serving hospitals were less likely to undergo surgical intervention. Furthermore, minority patients treated at non-minority-serving hospitals also had a decreased likelihood of surgery, though to a lesser extent. Surgery was associated with improved overall survival, regardless of minority status or hospital type.
Article
Oncology
Mathias E. Palmer, Jennifer J. Gile, Michael H. Storandt, Zhaohui Jin, Tyler J. Zemla, Nguyen H. Tran, Amit Mahipal
Summary: The use of lenvatinib following immunotherapy has shown favorable clinical outcomes in patients with advanced hepatocellular carcinoma, serving as a viable second-line therapy.
Article
Oncology
Michael H. Storandt, Kara R. Rogen, Anushka Iyyangar, Rylie R. Schnell, Jessica L. Mitchell, Joleen M. Hubbard, Frank A. Sinicrope, Aminah Jatoi, Amit Mahipal, Qian Shi, Zhaohui Jin
Summary: Rates of early-onset colorectal cancer have increased, with about one-quarter of cases being associated with a hereditary cancer syndrome. This study found that approximately one in four patients with early-onset colorectal cancer had a pathogenic germline variant, including 8.3% with Lynch syndrome. Similar rates of detection of pathogenic germline variants were seen in patients with average-onset colorectal cancer. This study underscores the importance of genetic testing for all patients with colorectal cancer, especially those with early-onset.
Article
Oncology
Nirosha D. Perera, Tiffany R. Bellomo, Walker M. Schmidt, Henry K. Litt, Margaret Shyu, MaKenna A. Stavins, Max M. Wang, Alexander Bell, Massoud Saleki, Katherine I. Wolf, Ruxandra Ionescu, Jacqueline J. Tao, Sunjong Ji, Ryan M. O'Keefe, Matthew Pun, Jordan M. Takasugi, Jecca R. Steinberg, Ronald S. Go, Brandon E. Turner, Amit Mahipal
Summary: This study evaluated the representation of female participants in US oncology clinical trials and found that females were underrepresented in surgical and invasive trials. The representation of females varied among different cancer sites, with some types of trials and industry-funded trials showing better female representation. It is important to consider female representation when interpreting trial results.