Review
Oncology
Mojun Zhu, Zhaohui Jin, Joleen M. Hubbard
Summary: Microsatellite instability (MSI) is a genetic predisposition to DNA damage, detectable through sequencing or immunohistochemistry, and associated with a high neoantigen load and favorable response to immune checkpoint inhibitors (ICIs). In gastrointestinal cancers, MSI serves as a predictive biomarker for ICIs with varying clinical utility depending on tumor type, potentially explained by the complex tumor microenvironment. This review explores the predictive and prognostic value of MSI in non-colorectal cancers of the digestive system and strategies to overcome immunotherapy resistance.
Article
Cell Biology
Aya Shinozaki-Ushiku, Akiko Kunita, Akiko Iwasaki, Moe Kato, Sho Yamazawa, Hiroyuki Abe, Tetsuo Ushiku
Summary: This study aimed to clarify the detailed MSI profiles of non-colorectal gastrointestinal cancers and investigate the differences from colorectal cancers. The results showed that MSI testing is applicable to non-colorectal gastrointestinal cancers, but a subset of cases may yield false-negative results, emphasizing the need for careful interpretation and analysis of results.
Article
Oncology
Yousun Chung, Soo Kyung Nam, Ho Eun Chang, Cheol Lee, Gyeong Hoon Kang, Hye Seung Lee, Kyoung Un Park
Summary: The study evaluated an experimental eight marker-panel for accurate determination of microsatellite instability (MSI) status in cancer patients. The testing showed high concordance with IHC analysis, with LMR markers demonstrating higher sensitivity and larger shifts compared to conventional markers in gastric and endometrial cancers. Further validation with larger sample sizes is needed for these LMR markers.
Article
Biology
Paulina Rzasa, Sarah Whelan, Pooyeh Farahmand, Hong Cai, Inna Guterman, Raquel Palacios-Gallego, Shanthi S. Undru, Lauren Sandford, Caleb Green, Catherine Andreadi, Maria Mintseva, Emma Parrott, Hong Jin, Fiona Hey, Susan Giblett, Nicolas B. Sylvius, Natalie S. Allcock, Anna Straatman-Iwanowska, Roberto Feuda, Cristina Tufarelli, Karen Brown, Catrin Pritchard, Alessandro Rufini
Summary: BRAF mutations occur early in serrated colorectal cancers, but their long-term influence on tissue homeostasis is poorly characterized. Short-term and long-term expression of Braf(V600E) in the intestinal tissue perturbs the homeostasis of intestinal epithelial cells, impairs differentiation of enterocytes, and leads to persistent transcriptional reprogramming.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rimma S. Mulkidjan, Evgeniya S. Saitova, Elena V. Preobrazhenskaya, Karimat A. Asadulaeva, Mikhail G. Bubnov, Ekaterina A. Otradnova, Darya M. Terina, Sofia S. Shulga, Darya E. Martynenko, Maria V. Semina, Evgeniya V. Belogubova, Vladislav I. Tiurin, Priscilla S. Amankwah, Aleksandr S. Martianov, Evgeny N. Imyanitov
Summary: This study conducted a comprehensive analysis of gene rearrangements in tumors with microsatellite instability (MSI). Gene fusions were detected in colorectal carcinomas (CRCs), gastric cancers (GCs), and endometrial cancers (ECs), but not in cervical carcinomas (CCs), pancreatic cancers (PanCs), cholangiocarcinomas (ChCs), and ovarian cancers (OCs). The frequency of gene rearrangements was highest in KRAS/NRAS/BRAF wild-type CRCs. There was a higher frequency of translocations in CRC patients aged above 50 years, particularly in tumors with normal KRAS/NRAS/BRAF status.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Takahiro Utsumi, Shin'ichi Miyamoto, Takahiro Shimizu, Kasumi Yokogawa, Yuki Nakanishi, Mitsuhiro Nikaido, Ayako Hirata, Miyu Nishida, Ikuo Aoyama, Tomoko Okuno, Akihiko Yoshizawa, Akihiro Kaneda, Yoshiharu Sakai, Chiharu Kawanami, Hiroshi Seno
Summary: Spontaneous regression in colorectal cancer is rare and often associated with specific endoscopic characteristics, lack of DNA mismatch repair proteins, and a deficiency in mismatch repair (dMMR). The activation of anti-tumor host immune responses through increased tumor-infiltrating lymphocytes may play a role in the spontaneous regression of colorectal cancer.
DIGESTIVE ENDOSCOPY
(2021)
Letter
Oncology
Hassan Mohammed Abushukair, Sara Mu'amar Zaitoun, Anwaar Saeed
Summary: Colorectal cancer (CRC) is a highly dangerous malignancy, and the BRAF(V600E) mutation, a common driver mutation in CRC, has been linked to immune status in the tumor microenvironment. However, current research has focused predominantly on macrophage polarity and cytokine levels, neglecting other immune factors. Therefore, a more comprehensive observation of immune activity may lead to more meaningful practical findings.
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
(2022)
Article
Oncology
Roel M. M. Bogie, Chantal M. C. le Clercq, Quirinus J. M. Voorham, Martijn Cordes, Daoud Sie, Christian Rausch, Evert van den Broek, Sara D. J. de Vries, Nicole C. T. van Grieken, Robert G. Riedl, Prapto Sastrowijoto, Ernst-Jan Speel, Rein Vos, Bjorn Winkens, Manon van Engeland, Bauke Ylstra, Gerrit A. Meijer, Ad A. M. Masclee, Beatriz Carvalho
Summary: PCCRCs are more commonly located proximally, non-polypoid appearing, early stage, and poorly differentiated compared to DCRCs. They also show significantly less 18q loss and are more commonly CIMP high and MSI. Molecular features associated with sessile serrated lesions and non-polypoid colorectal neoplasms may contribute to the development of PCCRCs.
BRITISH JOURNAL OF CANCER
(2022)
Editorial Material
Cell Biology
Gayathri Anandappa, Michael J. Overman
Summary: In a recent study, Amodio and colleagues discovered a method to modulate immunosurveillance in colorectal tumors by manipulating DNA mismatch repair heterogeneity. They found that enriching the MMR deficient component using 6-thioguanine can improve tumor control in murine models.
CELL REPORTS MEDICINE
(2023)
Article
Multidisciplinary Sciences
Ilya G. Serebriiskii, Valery Pavlov, Rossella Tricarico, Grigorii Andrianov, Emmanuelle Nicolas, Mitchell Parker, Justin Newberg, Garrett Frampton, Joshua E. Meyer, Erica A. Golemis
Summary: Loss or dysfunction of the PTEN tumor suppressor gene can activate pro-tumorigenic signaling pathways. In this study, the authors analyze sequencing data from a large cohort of colorectal cancer patients with PTEN mutations and identify distinct patterns of associations with genomic and clinical features.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Violaine Randrian, Camille Evrard, David Tougeron
Summary: A defective mismatch repair system leads to microsatellite instability, resulting in high mutation burden in tumors, with some mutations producing neo-antigens that trigger anti-tumoral immune response. Non-metastatic MSI tumors have high immune infiltrates and good prognosis, while metastatic MSI tumors, having evaded immune response, are associated with poor prognosis and chemoresistance. Immune checkpoint inhibitors (ICI) are effective in dMMR/MSI mCRC, but some patients may develop primary or secondary resistance, prompting the development of strategies targeting other immune checkpoints or utilizing vaccination and modification of microbiota to overcome resistance.
Review
Oncology
Simon Manuel Tria, Matthew E. Burge, Vicki L. J. Whitehall
Summary: More than a third of colorectal cancers have a KRAS mutation, posing a challenge for the development of direct targeting inhibitors. Recent advancements have led to the development of new generation inhibitors specifically targeting the G12C KRAS mutation, such as Adagrasib and Sotorasib. Therapeutic regimens are being developed to address resistance to these inhibitors and improve treatment outcomes.
Article
Gastroenterology & Hepatology
Claire Boyer, David Sefrioui, Romain Cohen, Romain Chautard, Marine Perrier, Hugo Lebrun, Gael Goujon, Vincent Hautefeuille, Marie Dior, Thomas Walter, Florence Mary, Silvain Manfredi, Francois-Xavier Caroli-Bosc, Baptiste Cervantes, Romain Coriat, Elise Deluche, Aziz Zaanan, Raphael Olivier, Olivier Bouche, Guillaume Piessen, Thierry Lecomte, Christophe Louvet, Pierre Michel, Thomas Aparicio, Thierry Andre, Julien Taieb, Violaine Randrian, David Tougeron
Summary: This French multicenter study evaluated the overall survival of patients with dMMR/MSI digestive non-colorectal tumors. The results showed that most tumors were oesophago-gastric or small bowel adenocarcinomas and were at a localized stage at diagnosis. Patients with localized tumors and R0 resection had a median overall survival of 134.0 +/- 64.2 months. Overall, dMMR/MSI digestive non-colorectal tumors have a good prognosis, but advanced tumors treated with standard chemotherapy have a poor prognosis.
DIGESTIVE AND LIVER DISEASE
(2023)
Article
Medicine, General & Internal
Bill H. Diplas, Ryan Ptashkin, Joanne F. Chou, Shalom Sabwa, Michael B. Foote, Benoit Rousseau, Guillem Argiles, James Robert White, Caitlin M. Stewart, Kelly Bolton, Sree B. Chalasani, Avni M. Desai, Zoe Goldberg, Ping Gu, Jia Li, Marina Shcherba, Alice Zervoudakis, Andrea Cercek, Rona Yaeger, Neil H. Segal, David H. Ilson, Geoffrey Y. Ku, Ahmet Zehir, Marinela Capanu, Yelena Y. Janjigian, Luis A. Diaz, Steven B. Maron
Summary: This retrospective cohort study analyzed 633 patients with metastatic gastrointestinal tract cancer and found that clonal hematopoiesis (CH) was associated with survival outcomes. However, the association with cancer therapy efficacy and toxicity has not been established.
Article
Oncology
Chung Ryul Oh, Jeong Eun Kim, Yong Sang Hong, Sun Young Kim, Joong Bae Ahn, Ji Yeon Baek, Myung-Ah Lee, Myoung Joo Kang, Sang Hee Cho, Seung-Hoon Beom, Tae Won Kim
Summary: The aim of this study was to evaluate the clinical efficacy of durvalumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) or polymerase epsilon (POLE)-mutated metastatic or unresectable colorectal cancer (mCRC). The results showed that durvalumab demonstrated promising clinical activity with encouraging response rates and satisfactory survival outcomes in these patients.
INTERNATIONAL JOURNAL OF CANCER
(2022)
