Article
Oncology
Camilla Di Dio, Giorgio Bogani, Violante Di Donato, Ilaria Cuccu, Ludovico Muzii, Lucia Musacchio, Giovanni Scambia, Domenica Lorusso
Summary: Endometrial cancer is a heterogeneous disease with specific genomic, molecular, and biological features. Immune checkpoint inhibitors and tyrosine kinase inhibitors have shown promising results in the treatment of advanced or recurrent endometrial cancer. The combination of pembrolizumab and lenvatinib has become the new standard second-line treatment, regardless of the MMR status. Further studies are exploring the use of immune checkpoint inhibitors and PARP inhibitors in combination therapy.
GYNECOLOGIC ONCOLOGY
(2023)
Article
Oncology
P. -S. Kok, Y. C. Antill, C. L. Scott, C. K. Lee
Summary: This meta-analysis showed that single-agent ICI had significantly higher objective response rate and longer progression-free survival in patients with dMMR compared to those with pMMR in advanced endometrial cancer.
Review
Oncology
Francisco Cezar Aquino de Moraes, Eric Pasqualotto, Lucca Moreira Lopes, Maria Eduarda Cavalcanti Souza, Anna Luiza Soares de Oliveira Rodrigues, Artur Menegaz de Almeida, Carlos Stecca, Marianne Rodrigues Fernandes, Ney Pereira Carneiro dos Santos
Summary: The combination of PD-1/PD-L1 inhibitors with carboplatin and paclitaxel significantly improves progression-free survival and overall survival in patients with advanced or recurrent endometrial cancer, particularly for those with mismatch repair deficiency and high microsatellite instability.
Article
Health Care Sciences & Services
Kiyoka Sawada, Kentaro Nakayama, Sultana Razia, Hitomi Yamashita, Tomoka Ishibashi, Masako Ishikawa, Kosuke Kanno, Seiya Sato, Satoru Nakayama, Yoshiro Otsuki, Satoru Kyo
Summary: Type II endometrial cancer (EC) is aggressive, difficult to detect in later stages, and often resistant to standard therapies. This study evaluated the potential of immune checkpoint inhibitors as a therapeutic strategy for patients with mismatch repair-deficient (dMMR) tumors, finding that dMMR was significantly associated with increased expression of immune checkpoint molecules PD-L1 and CD8+. These results suggest that anti-PD-L1/PD-1 antibodies may effectively treat dMMR type II EC, and the presence of dMMR could serve as a biomarker for positive response to PD-1/PD-L1 immunotherapy.
Article
Oncology
Neil A. J. Ryan, Thomas D. J. Walker, James Bolton, Natalja ter Haar, Tom Van Wezel, Mark A. Glaire, David N. Church, D. Gareth Evans, Tjalling Bosse, Emma J. Crosbie
Summary: Endometrial cancers can arise from somatic events or Lynch syndrome, with distinct molecular and pathological features between the two. These differences may lead to heterogenous responses to treatments and clinical trial outcomes.
Article
Health Care Sciences & Services
Abdul K. Siraj, Sandeep Kumar Parvathareddy, Padmanaban Annaiyappanaidu, Wael Haqawi, Maha Al-Rasheed, Hadeel M. AlManea, Hussah F. AlHussaini, Fouad Al-Dayel, Khawla S. Al-Kuraya
Summary: This study in Middle Eastern CRC patients showed that PD-L1 expression is associated with aggressive clinic-pathological features, MMR deficiency, and BRAF mutation, and it serves as an independent prognostic marker for overall survival. These findings suggest that PD-L1 expression could be a useful biomarker for predicting poor prognosis in Middle Eastern CRC patients, particularly those with MMR deficient tumors.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Letter
Medicine, General & Internal
Mehmet Copur, Soe Min Tun, Randall A. Duckert
Summary: In this study, Cercek et al. report a complete clinical response in 12 patients with locally advanced, mismatch repair-deficient rectal cancer after 6 months of neoadjuvant treatment with single-agent programmed death 1 (PD-1) blockade. The mismatch-repair status of the patients was determined using chromogenic immunohistochemical assay, and comprehensive genomic analyses were performed using next-generation sequencing assay.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Oncology
Romy Walker, Khalid Mahmood, Julia Como, Mark Clendenning, Jihoon E. Joo, Peter Georgeson, Sharelle Joseland, Susan G. Preston, Bernard J. Pope, James M. Chan, Rachel Austin, Jasmina Bojadzieva, Ainsley Campbell, Emma Edwards, Margaret Gleeson, Annabel Goodwin, Marion T. Harris, Emilia Ip, Judy Kirk, Julia Mansour, Helen Mar Fan, Cassandra Nichols, Nicholas Pachter, Abiramy Ragunathan, Allan Spigelman, Rachel Susman, Michael Christie, Mark A. Jenkins, Rish K. Pai, Christophe Rosty, Finlay A. Macrae, Ingrid M. Winship, Daniel D. Buchanan, ANGELS Study
Summary: This study examined the effectiveness of Lynch syndrome-specific tumor features in classifying MMR gene variants of uncertain clinical significance. The findings confirmed that identifying these features can improve the classification of MMR variants and enable optimal clinical care.
Article
Biotechnology & Applied Microbiology
Xiaojuan Liu, Hui Ma, Lisha Ma, Kun Li, Yanhua Kang
Summary: This study explored the potential function of METTL5 in UCEC and verified the relationship between deficient DNA mismatch repair and METTL5. The results showed that METTL5 expression was increased in UCEC tumor tissue and UCEC patients with high METTL5 expression had worse prognostic outcomes. Knocking down METTL5 weakened UCEC proliferation, increased apoptosis, and influenced the development and prognosis of UCEC through regulating MMR protein levels.
Article
Oncology
Jianxia Li, Cheng Wu, Huabin Hu, Ge Qin, Xueqian Wu, Fan Bai, Jianwei Zhang, Yue Cai, Yan Huang, Chao Wang, Jiaqi Yang, Yizhao Luan, Zehang Jiang, Jiayu Ling, Zehua Wu, Yaoxu Chen, Zhi Xie, Yanhong Deng
Summary: Immune checkpoint inhibitor therapy induces complete responses in mismatch repair-deficient and microsatellite instability-high colorectal cancers. The mechanism of pathological complete response to immunotherapy is not fully understood. Single-cell RNA sequencing was used to study the dynamics of immune and stromal cells in patients with colorectal cancer receiving neoadjuvant PD-1 blockade. Proinflammatory features in the tumor microenvironment affect the CD8+ T cells and other immune cell populations, mediating the persistence of residual tumors. The study provides insights into the mechanism of successful immune checkpoint inhibitor therapy and potential targets for improving treatment efficacy.
Article
Immunology
Yu-Ting Ma, Fang Hua, Xiu-Ming Zhong, Ying-Jie Xue, Jia Li, Yi-Cong Nie, Xue-Dong Zhang, Ji-Wei Ma, Cun-Hu Lin, Hao-Zhuang Zhang, Wei He, Dan Sha, Miao-Qing Zhao, Zhi-Gang Yao
Summary: This study provides comprehensive real-world data on the characteristics of urothelial carcinoma with deficient mismatch repair (dMMR UC) in Chinese patients, including incidence, clinicopathological features, molecular landscape, and biomarkers for predicting the efficacy of PD-1/PD-L1 inhibitors. The study found a higher incidence of dMMR UC in the upper urinary tract compared to the bladder, frequent mutations in KMT2D and KMT2C genes, and confirmed Lynch syndrome in some cases. Additionally, the study revealed that the density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients and that some patients with negative PD-L1 expression responded positively to immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Kaysia Ludford, Romain Cohen, Magali Svrcek, Wai Chin Foo, Raphael Colle, Yann Parc, Jane Varkey Thomas, Van Karlyle Morris, Scott Kopetz, George J. Chang, Michael Overman, Thierry Andre
Summary: This study found that residual radiographic tumor following anti-PD1 therapy may not require systematic resection and pathological complete response may be feasible for dMMR mCRC patients. Further larger prospective studies are needed to confirm these findings.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Medicine, General & Internal
Andrea Cercek, Melissa Lumish, Jenna Sinopoli, Jill Weiss, Jinru Shia, Michelle Lamendola-Essel, Imane H. El Dika, Neil Segal, Marina Shcherba, Ryan Sugarman, Zsofia Stadler, Rona Yaeger, J. Joshua Smith, Benoit Rousseau, Guillem Argiles, Miteshkumar Patel, Avni Desai, Leonard B. Saltz, Maria Widmar, Krishna Iyer, Janie Zhang, Nicole Gianino, Christopher Crane, Paul B. Romesser, Emmanouil P. Pappou, Philip Paty, Julio Garcia-Aguilar, Mithat Gonen, Marc Gollub, Martin R. Weiser, Kurt A. Schalper, Luis A. Diaz
Summary: This study found that mismatch repair-deficient, locally advanced rectal cancer is highly sensitive to PD-1 blockade. Additionally, no adverse events of grade 3 or higher have been reported, and no cases of progression or recurrence have been observed. Longer follow-up is needed to assess the duration of response.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Oncology
Shuangshuang Zhao, Lingli Chen, Yuqin Zang, Wenlu Liu, Shiqi Liu, Fei Teng, Fengxia Xue, Yingmei Wang
Summary: Lynch syndrome (LS) is caused by germline pathogenic variants in mismatch repair (MMR) genes, leading to LS-associated endometrial cancer (LS-EC) which has specific clinicopathologic features. Screening, diagnosis, surveillance, prevention and treatment for LS-EC have significantly advanced, with recommendations for universal LS screening among EC patients.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Review
Immunology
Yuedi Zhang, Qiulin Cui, Manman Xu, Duo Liu, Shuzhong Yao, Ming Chen
Summary: Immunotherapies have revolutionized cancer treatment, but recurrent ovarian cancer remains difficult to treat. Recurrent ovarian cancer is a cold tumor with limited response to immunotherapy. However, combining immunotherapy with other treatments may improve outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
