Article
Oncology
Farzana Jasmine, Zahidul Haq, Mohammed Kamal, Maruf Raza, Gustavo da Silva, Katrina Gorospe, Rupash Paul, Patrick Strzempek, Habibul Ahsan, Muhammad G. Kibriya
Summary: This study explored the association between DNA methylation and microsatellite instability (MSI) in colorectal cancer (CRC), finding a higher number of methylated genes in tumor tissue of patients with MSI. The results indicate a link between MSI and tumor DNA methylation in the pathogenesis of CRC. The study also suggests the potential use of specific immune checkpoint inhibitors (CTLA4 and HAVCR2 inhibitors) in CRC with MSI.
Review
Oncology
Vito Amodio, Gianluca Mauri, Nicole M. Reilly, Andrea Sartore-Bianchi, Salvatore Siena, Alberto Bardelli, Giovanni Germano
Summary: A subset of colorectal cancers with mismatch repair deficiency are sensitive to immune checkpoint inhibitors, but some patients show primary resistance or develop acquired resistance. Changes in the Wnt and JAK-STAT signaling pathways, as well as alterations in the antigen presentation machinery, are associated with resistance to CPIs in these patients. Understanding the mechanistic basis of immune evasion in CRC provides rationale for innovative strategies to increase the subset of patients benefiting from CPIs.
Review
Pharmacology & Pharmacy
Chandra Kishore, Priyanka Bhadra
Summary: 5-Fluorouracil (5-FU) is the first-line chemotherapy drug for colorectal cancer, but patients often develop resistance to it. Immunotherapy has shown promise in treating colorectal cancer, especially in providing long-term remission for some metastatic CRC patients.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Edouard Auclin, Perrine Vuagnat, Cristina Smolenschi, Julien Taieb, Jorge Adeva, Laetitia Nebot-Bral, Marta Garcia de Herreros, Rosario Vidal Tocino, Federico Longo-Munoz, Yola El Dakdouki, Patricia Martin-Romano, Lydia Gaba, Tamara Sauri, Helena Oliveres, Eduardo Castanon, Rocio Garcia-Carbonero, Benjamin Besse, Christophe Massard, Laura Mezquita, Antoine Hollebecque
Summary: The Lung Immune Prognostic Index (LIPI) is a prognostic factor for ICI efficacy in dMMR tumors, with patients having a Poor LIPI showing more disease progression and shorter survival. LIPI could be considered as a stratification factor for future trials.
Article
Immunology
Wenyue Zhou, Yuwen Zhou, Cheng Yi, Xinyao Shu, Guixia Wei, Xiaorong Chen, Xudong Shen, Meng Qiu
Summary: Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) is a predictive biomarker for immune checkpoint inhibitors (ICIs) in colorectal and non-colorectal cancer populations, but not all MSI-H tumors respond to ICIs. Some patients develop hyperprogression after ICI treatment, with unclear mechanisms.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Agnieszka Kula, Miriam Dawidowicz, Sylwia Mielcarska, Pawel Kiczmer, Hanna Skiba, Malgorzata Krygier, Magdalena Chrabanska, Jerzy Piecuch, Monika Szrot, Julia Robotycka, Blazej Ochman, Bogumila Strzalkowska, Zenon Czuba, Elzbieta Swietochowska, Dariusz Waniczek
Summary: This study aims to investigate the correlation between HHLA2 levels and various parameters in colorectal cancer (CRC). The results demonstrate that HHLA2 is highly expressed in CRC tumor tissues compared to adjacent noncancerous tissues. The study provides valuable insights into the role of HHLA2 as a stimulatory and inhibitory immune checkpoint in CRC and suggests the potential therapeutic value of the HHLA2-KIR3DL3/TMIGD2 pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ahui Fan, Boda Wang, Xin Wang, Yongzhan Nie, Daiming Fan, Xiaodi Zhao, Yuanyuan Lu
Summary: Immunotherapy has shown significant progress in treating colorectal cancer, with the approval of two PD-1 antibodies and successful outcomes in first-line treatment reported in the past two years. Attention is also paid to predictive biomarkers for immunotherapy, with promising results in different types of colorectal cancer treatments.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Oncology
Julien Taieb, Lina Sayah, Kathrin Heinrich, Volker Kunzmann, Alice Boileve, Geert Cirkel, Sara Lonardi, Benoist Chibaudel, Anthony Turpin, Tamar Beller, Vincent Hautefeuille, Caterina Vivaldi, Thibault Mazard, Lucile Bauguion, Monica Niger, Gerald W. Prager, Clelia Coutzac, C. Benedikt Westphalen, Edouard Auclin, Lorenzo Pilla
Summary: This multi-institutional analysis evaluated the efficacy and tolerability of ICIs in a large cohort of patients with MSI/dMMR PDAC. The results showed that ICIs had significant efficacy and tolerability in these patients, suggesting they could be a viable treatment option.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Oncology
Qianyu Wang, Xiaofei Shen, Gang Chen, Junfeng Du
Summary: Immunotherapy, particularly immune checkpoint inhibitors (ICIs), offers hope for patients with failed multiline therapy in cancer treatment. However, the benefit is limited to a small subset of patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Resistance to ICIs is observed in 45-60% of dMMR/MSI-H mCRC patients, indicating potential unknown pathways mediating immune escape. Mismatch repair-proficient (pMMR) or microsatellite-stable (MSS) mCRC patients do not benefit from ICIs. This review discusses the mechanisms of action and current status of ICIs in CRC, as well as the mechanisms of primary and acquired resistance and potential therapeutic strategies to overcome resistance in the clinic.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Alejandro Olivares-Hernandez, Edel del Barco Morillo, Carmen Parra Perez, Jose Pablo Miramontes-Gonzalez, Luis Figuero-Perez, Teresa Martin-Gomez, Roberto Escala-Cornejo, Lorena Bellido Hernandez, Rogelio Gonzalez Sarmiento, Juan Jesus Cruz-Hernandez, Maria Dolores Ludena de la Cruz
Summary: Mutations in the MMR system genes play a significant role in the response to and survival of ICIs in NSCLC. Patients with deficient MMR expression demonstrated more severe toxicity to ICIs. Assessing MMR system genes is crucial for personalized immunotherapy treatments.
Article
Immunology
Qing Wu, Ziming Wang, Yang Luo, Xianhe Xie
Summary: This study aimed to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs)-based therapy in pMMR/non-MSI-H mCRC. The study found that ICIs-based combination therapy, especially when combined with first-line anti-VEGF agent plus chemotherapy, showed good efficacy and controllable toxicity in pMMR/non-MSI-H mCRC.
Review
Oncology
Aristeidis E. Boukouris, Maria Theochari, Dimitra Stefanou, Alexandros Papalambros, Evangelos Felekouras, Helen Gogas, Dimitrios C. Ziogas
Summary: Immune-checkpoint inhibitors have shown potential in the treatment of metastatic colorectal cancer. Pembrolizumab is approved as a preferred option in first-line treatment, while nivolumab alone or in combination with ipilimumab is an alternative option. In subsequent lines, these immunotherapeutic regimens, as well as dostarlimab-gxly, are recommended for chemo-resistant mCRC patients who have not received ICIs previously.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Review
Gastroenterology & Hepatology
Elaine Tan, Ibrahim Halil Sahin
Summary: Immune checkpoint inhibitor (ICI) therapy has changed the treatment approach for MMR-D/MSI-H CRC patients, with a focus on recent data regarding ICI use, potential biomarkers, and innovative therapeutic approaches. Medical experts believe that more novel immunomodulatory agents and targeted therapies for immune resistance pathways are needed for MMR-D/MSI-H CRC patients who have been treated with ICI therapy.
EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Oncology
Mifen Chen, Zhenghang Wang, Zimin Liu, Ning Liu, Weijia Fang, Hangyu Zhang, Xuan Jin, Jiayi Li, Weifeng Zhao, Huajun Qu, Fanghua Song, Zhiwei Chang, Yi Li, Yong Tang, Chunlei Xu, Xiaotian Zhang, Xicheng Wang, Zhi Peng, Jinping Cai, Jian Li, Lin Shen
Summary: This study retrospectively evaluated the efficacy of anti-PD1/PD-L1 plus other drug therapy compared to chemotherapy with or without targeted therapy in MSI/dMMR gastrointestinal cancer patients who had progressed on prior anti-PD1/PD-L1 monotherapy. The results showed that anti-PD1/PD-L1 plus other drug therapy significantly improved disease control rate, progression-free survival, and overall survival, with a numerically higher objective response rate. These findings are promising and should be further confirmed in prospective trials.
Article
Oncology
Elena Bolzacchini, Laura Libera, Sarah E. Church, Nora Sahnane, Raffaella Bombelli, Nunzio Digiacomo, Monica Giordano, Guido Petracco, Fausto Sessa, Carlo Capella, Daniela Furlan
Summary: BRAF mutant metastatic colorectal cancers (BRAF-mCRCs) have a poor prognosis and show limited response to standard chemotherapy and BRAF inhibitors. This study identifies a subset of BRAF-mCRCs with a hot/inflamed profile that may respond to immunotherapy. The presence of microsatellite instability (MSI) and CD8+ tumor-infiltrating lymphocytes (TILs) are associated with immunotherapy response. Gene expression profiles can predict response to immune checkpoint inhibitors in BRAF-mCRCs.
Review
Oncology
Chloe S. Lalonde, Linyuan Wang, Brian Quigley, Pretesh Patel, Shishir K. Maithel, Bassel F. El-Rayes, Mehmet Akce
Summary: Carcinosarcoma of the pancreas is a rare malignancy with limited treatment options. This case report demonstrates successful treatment with neoadjuvant FOLFIRINOX followed by chemoradiation, resulting in partial pathological response and 15 months of disease-free survival. Further research is needed to establish optimal systemic therapies for this rare clinical entity.
CHINESE CLINICAL ONCOLOGY
(2022)
Article
Oncology
Rami P. Atallah, Yining Zhang, Katerina Zakka, Renjian Jiang, Zhonglu Huang, Walid L. Shaib, Maria Diab, Mehmet Akce, Christina Wu, Bassel F. El-Rayes, Olatunji B. Alese
Summary: This study investigated the impact of local therapy on survival in patients with anal SCCa. The results showed that local therapy (primary tumor resection or palliative radiation) improved the survival rate of patients, while chemotherapy had poorer efficacy. Age, gender, insurance status, and site of cancer occurrence were poor prognostic factors.
JOURNAL OF GASTROINTESTINAL ONCOLOGY
(2022)
Review
Oncology
Ruveyda Ayasun, Turcin Saridogan, Ola Gaber, Ibrahim Halil Sahin
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and is often diagnosed at advanced stages. Systemic chemotherapy is the standard treatment, but advancements in targeted therapy and immunotherapy have been limited. Recent studies have identified potential therapeutic targets and opportunities for PDAC patients.
CLINICAL COLORECTAL CANCER
(2023)
Article
Cardiac & Cardiovascular Systems
Kumar Mukherjee, Mohammad Elsayed, Eshani Choksi, Mohammed F. Loya, Richard Duszak, Mehmet Akce, Bill S. Majdalany, Zachary L. Bercu, Mircea Cristescu, Nima Kokabi
Summary: This study examines the association between metformin use and overall survival in patients with hepatocellular carcinoma (HCC) undergoing image-guided liver-directed therapy (LDT). The results show that metformin use is associated with longer survival in patients undergoing tumor ablation and TACE.
CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Charan Thej Reddy Vegivinti, Cyndi Gonzales Gomez, Masood Syed, Morgan Ferrell, Svea Cheng, Aatur Singhi, Anwaar Saeed, Ibrahim Halil Sahin
Summary: FDA approved pembrolizumab for patients with unresectable or metastatic solid tumors with tumor mutational burden (TMB) = 10. However, the clinical implications of this cutoff for patients with microsatellite stable (MSS) metastatic colorectal cancer (CRC) are still debatable. This review discusses the tissue agnostic approval of pembrolizumab, its efficacy, and clinical relevance in managing MSS CRC patients with high TMB. The review also elaborates on molecular subgroups of MSS CRC that influence the response to immune checkpoint inhibitors.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Mehmet Akce, Bassel F. El-Rayes, Narendra Wajapeyee
Summary: Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide, with a low survival rate for unresectable HCC. The liver tumor microenvironment is immunosuppressive, and immune checkpoint inhibitors (ICIs) have shown promise in enhancing antitumor immunity. However, single-agent ICIs have limited effectiveness in HCC, leading to research exploring combinatorial approaches, such as combining ICIs with epigenetic inhibitors, to improve outcomes. This review discusses current ICI treatments for HCC, their mechanisms of action, and the potential of combining ICIs with epigenetic inhibitors for treating immune-cold HCC.
Article
Oncology
Xiao-Dong Jiao, Bao-Dong Qin, Zhan Wang, Ke Liu, Ying Wu, Yan Ling, Wen-Xing Qin, Miao-Miao Wang, Ling-Yan Yuan, Savio George Barreto, Anthony W. Kim, Kimberley Mak, Hao Li, Yuan-Yuan Xu, Xiao-Ming Qiu, Min Wu, Min Jin, Li-Chao Xu, Yi Zhong, Hui Yang, Xue-Qin Chen, Yu Zeng, Jun Shi, Wen-Yu Zhu, Qing-Qing Ding, Wei Jia, Su-Fen Liu, Jun-Jing Zhou, Hong Shen, Shi-Hua Yao, Zhao-Ji Guo, Ting Li, Pei-Juan Zhou, Xue-Wei Dong, Wen-Feng Lu, Robert L. Coleman, Mehmet Akce, Cherif Akladios, Francesco Puccetti, Yuan-Sheng Zang
Summary: This study evaluated the effects of molecular-guided targeted therapy on intractable cancer and investigated the epidemiology of druggable gene alterations in the Chinese population. The results showed significant clinical benefit of molecular-guided targeted therapy for intractable cancer and supported the feasibility of this approach in different cancer types.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Ibrahim Halil Sahin, Janie Zhang, Turcin Saridogan, Vikram Gorantla, John Rhree, Monica Malhotra, Roby Thomas, Dennis Hsu, Anwaar Saeed
Summary: Immune checkpoint inhibitors have revolutionized the treatment of mismatch repair-deficient/microsatellite instability-high colorectal cancer. The unique molecular features of this subtype of cancer create an ideal framework for T-cell priming and antitumor immunity. Recent advancements in ICI-based therapies have shown promising results in both early-stage colon and rectal cancer.
JCO ONCOLOGY PRACTICE
(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)
Article
Oncology
Daniel Clausing, Mackenzie E. Fowler, Christian Harmon, Abigail Tucker, Darryl Outlaw, Mehmet Akce, Bassel El-Rayes, Smith Giri, Grant R. Williams
Summary: This study found that older adults with inadequate emotional support have worse physical and mental health-related quality of life and higher odds of depression compared to those with adequate support.
Article
Gastroenterology & Hepatology
Lana Khalil, Zhonglu Huang, Katerina Zakka, Renjian Jiang, McKenna Penley, Olatunji B. Alese, Walid L. Shaib, Christina Wu, Madhusmita Behera, Michelle D. Reid, Bassel F. El-Rayes, Mehmet Akce
Summary: This study aims to evaluate the clinicopathological features and overall survival of patients with pancreatic colloid carcinoma (CC). It was found that CC was more commonly diagnosed at stage I and had better overall survival than pancreatic ductal adenocarcinoma (PDAC) in all stages except stage III.
Review
Gastroenterology & Hepatology
Mehmet Akce, Bassel F. El-Rayes, Tanios S. Bekaii-Saab
Summary: Hepatocellular carcinoma (HCC) is rapidly becoming a leading cause of cancer-related mortality in the US. Current frontline systemic therapy options include sorafenib, lenvatinib, and atezolizumab/bevacizumab. The landscape of frontline HCC treatment is changing rapidly.
THERAPEUTIC ADVANCES IN GASTROENTEROLOGY
(2022)
Meeting Abstract
Oncology
Tony Z. Zhuang, Saima Muzahir, Kristina D. Murphy, Mehmet Akce, Olatunji B. Alese, Maria Diab Olumide B. Gbolahan, Walid Labib Shaib
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Manish Sharma, Babar Bashir, Dejan Juric, Erika P. Hamilton, Kyriakos P. Papadopoulos, Susanna Varkey Ulahannan, Geoffrey Shapiro, Vaibhav Sahai, Niharika B. Mettu, Monica M. Mita, Mehmet Akce, Jessica Tao, Graeme Hodgson, Nan Ke, Susan Henry, Sofia Paul, Neha Lodaya, Catherine Madigan, David A. Roth, Virginia Klimek
JOURNAL OF CLINICAL ONCOLOGY
(2022)
