Article
Oncology
Rabea Wagener, Carolin Walter, Franziska Auer, Deya Alzoubi, Julia Hauer, Ute Fischer, Julian Varghese, Martin Dugas, Arndt Borkhardt, Triantafyllia Brozou
Summary: Through whole-exome sequencing, we identified CHEK2 germline variants in 32/418 (7.7%) pediatric cancer patients, with 46.8% of them having leukemia. Functional analysis revealed that 5 pathogenic variants impaired CHK2 protein function. In conclusion, CHEK2 variants increase the risk for not only adult-onset but also pediatric cancer.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Oncology
Xiaoman Bi, Qing Zhang, Lei Chen, Dan Liu, Yueying Li, Xiaoxi Zhao, Ya Zhang, Liping Zhang, Jingkun Liu, Chaoyi Wu, Zhigang Li, Yunze Zhao, Honghao Ma, Gang Huang, Xin Liu, Qian-fei Wang, Rui Zhang
Summary: The study identified NBAS gene with high frequency mutation in HLH patients, indicating its potential role in the development of HLH through the lytic vesicle transport pathway.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Maja Louise Arendt, Sharadha Sakthikumar, Malin Melin, Ingegerd Elvers, Patricio Rivera, Majbritt Larsen, Sara Saellstrom, Frode Lingaas, Henrik Roennberg, Kerstin Lindblad-Toh
Summary: Biological features of neoplastic disease affecting mammary gland tissue are shared between canines and humans. Research performed in either species has translational value and early phase clinical trials performed in canines with spontaneous disease could be informative for human trials. This study identified PIK3CA as the most commonly mutated gene in canine mammary tumors, with mutations similar to human breast neoplasia. Other mutations in KRAS and PTEN were also identified. This data supports the validity of studying cancer in non-human species.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Abdul K. Siraj, Sandeep Kumar Parvathareddy, Nabil Siraj, Khadija Al-Obaisi, Saud M. Aldughaither, Hadeel M. AlManea, Hussah F. AlHussaini, Fouad Al-Dayel, Khawla S. Al-Kuraya
Summary: The study revealed that loss of ZNF677 protein expression is common in Middle Eastern CRC, and is associated with the severity of the tumor and lymph node metastasis. ZNF677 loss serves as an independent predictor of lymph node metastasis in CRC.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, General & Internal
Marwan G. Fakih, Lisa Salvatore, Taito Esaki, Dominik P. Modest, David P. Lopez-Bravo, Julien Taieb, Michalis V. Karamouzis, Erika Ruiz-Garcia, Tae-Won Kim, Yasutoshi Kuboki, Fausto Meriggi, David Cunningham, Kun-Huei Yeh, Emily Chan, Joseph Chao, Yaneth Saportas, Qui Tran, Chiara Cremolini, Filippo Pietrantonio
Summary: In this study, the combination of KRAS G12C inhibitor sotorasib and EGFR inhibitor panitumumab showed longer progression-free survival compared to standard treatment in patients with chemorefractory metastatic colorectal cancer.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Multidisciplinary Sciences
Abdul Khalid Siraj, Rong Bu, Tariq Masoodi, Sandeep Kumar Parvathareddy, Kaleem Iqbal, Wael Al-Haqawi, Hassan Al-Dossari, Saud Azam, Zeeshan Qadri, Padmanaban Annaiyappanaidu, Fouad Al-Dayel, Khawla Sami Al-Kuraya
Summary: RNF43 mutations are frequently found in Middle Eastern CRC, with a strong association with right-sided and sporadic MSI CRC, and no association with other clinical and pathological features.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Jeeshan Jiffry, Thongthai Thavornwatanayong, Devika Rao, Elisha J. Fogel, Durvanand Saytoo, Rishika Nahata, Hillary Guzik, Imran Chaudhary, Titto Augustine, Sanjay Goel, Radhashree Maitra
Summary: The study revealed that Pelareorep can enhance its propagation and oncolytic effect in colorectal cancer cells by regulating autophagy-related genes and proteins.
CLINICAL CANCER RESEARCH
(2021)
Article
Medicine, General & Internal
Rona Yaeger, Jared Weiss, Meredith S. Pelster, Alexander Spira, Minal Barve, Sai-Hong Ou, Ticiana A. Leal, Tanios S. Bekaii-Saab, Cloud P. Paweletz, Grace A. Heavey, James G. Christensen, Karen Velastegui, Thian Kheoh, Hirak Der-Torossian, Samuel J. Klempner
Summary: In this study, the researchers investigated the clinical efficacy of adagrasib in combination with cetuximab for heavily pretreated patients with metastatic colorectal cancer harboring mutant KRAS G12C. The results showed that the overall response rate was 19% in the adagrasib monotherapy group, with a median progression-free survival of 5.6 months, and 46% in the combination therapy group, with a median progression-free survival of 6.9 months. Both groups experienced reversible adverse events.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
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)
Review
Oncology
G. Patelli, F. Tosi, A. Amatu, G. Mauri, A. Curaba, D. A. Patane, A. Pani, F. Scaglione, S. Siena, A. Sartore-Bianchi
Summary: RAS oncogene is commonly mutated in cancer, particularly in metastatic colorectal cancer (mCRC), leading to poor prognosis and resistance to certain treatments. Recent advancements in specific KRAS(G12C) inhibitors have renewed interest in targeting this biomarker. Direct KRAS(G12C) inhibition is emerging as a promising strategy in mCRC and other solid malignancies, showing potential for improved treatment efficacy in the future.
Review
Oncology
Kristen K. Ciombor, John H. Strickler, Tanios S. Bekaii-Saab, Rona Yaeger
Summary: BRAF-mutated advanced colorectal cancer is a critical subset with prognostic and predictive implications. Standard therapies include bevacizumab and encorafenib, but resistance to targeted treatment remains a challenge.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Daniella C. N. Hall, Ralf A. Benndorf
Summary: PIK3CA mutations are common in cancer and associated with resistance to treatment and low survival rates. Aspirin may benefit patients with PIK3CA mutations, especially in colorectal cancer. This review aims to summarize and analyze the mechanisms and targets behind aspirin sensitivity in PIK3CA-mutated cancers.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Genetics & Heredity
Rebecca S. Tooze, Eduardo Calpena, Astrid Weber, Louise C. Wilson, Stephen R. F. Twigg, Andrew O. M. Wilkie
Summary: Craniosynostosis, a condition where the cranial sutures fuse prematurely, affects about 1 in 2000 children. While some cases are caused by known genetic variants or chromosomal abnormalities, there are many rare mutations in over 60 known genes. Genome sequencing is being used more frequently for diagnosing rare diseases, but the analysis of the data is time-consuming and requires a trade-off between sensitivity and precision. PanelApp, a crowd-sourced gene panel, helps prioritize variants in known disease genes and improve the detection of true-positive cases. Regular updates are necessary to avoid missing diagnoses for heterogeneous disorders like craniosynostosis.
Article
Oncology
Tomohiro Tate, Saki Matsumoto, Kensaku Nemoto, Matthias Leisegang, Satoshi Nagayama, Kazutaka Obama, Yusuke Nakamura, Kazuma Kiyotani
Summary: This study identified a shared neoantigen derived from FGFR3(Y373C) and demonstrated that immunotherapies targeting shared neoantigens are a promising approach for cancer treatment.
Article
Cell Biology
Gian Luca Rampioni Vinciguerra, Alessandra Dall'Acqua, Ilenia Segatto, Maria Chiara Mattevi, Francesca Russo, Andrea Favero, Roberto Cirombella, Giorgia Mungo, Davide Viotto, Javad Karimbayli, Margherita Pesce, Andrea Vecchione, Barbara Belletti, Gustavo Baldassarre
Summary: This study found that the expression of p27(kip1) is inversely correlated with the response to the CDK4/6 inhibitor Palbociclib in colorectal cancer patients, and investigated the mechanisms of resistance development and ways to overcome it.
CELL DEATH & DISEASE
(2021)
Review
Medicine, Research & Experimental
Sheema Hashem, Tayyiba Akbar Ali, Sabah Akhtar, Sabah Nisar, Geetanjali Sageena, Shahid Ali, Sharefa Al-Mannai, Lubna Therachiyil, Rashid Mir, Imadeldin Elfaki, Mohammad Muzaffar Mir, Farrukh Jamal, Tariq Masoodi, Shahab Uddin, Mayank Singh, Mohammad Haris, Muzafar Macha, Ajaz A. Bhat
Summary: Cancer is a major cause of death and a burden to healthcare system. Natural products, with their accessibility, applicability, and reduced cytotoxicity, have been an important source of anticancer drugs. They play a major role in cancer treatment by modulating cancer microenvironment and different signaling pathways, mainly cell death pathways and embryonic developmental pathways.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Endocrinology & Metabolism
Sandeep Kumar Parvathareddy, Abdul K. Siraj, Padmanaban Annaiyappanaidu, Nabil Siraj, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya
Summary: This study retrospectively analyzed 1283 patients with papillary thyroid carcinoma (PTC) and found a high incidence of bilateral multifocality. Bilateral multifocality was closely associated with clinical pathological characteristics such as age, gender, tumor size, and lymph node metastasis. It was also identified as an independent predictor of PTC recurrence. Therefore, patients with bilateral multifocal PTC may benefit from more frequent follow-up to detect recurrences earlier.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Pratheesh Kumar Poyil, Abdul K. Siraj, Divya Padmaja, Sandeep Kumar Parvathareddy, Roxanne Diaz, Saravanan Thangavel, Rafia Begum, Wael Haqawi, Falah Hassan Al-Mohanna, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya
Summary: This study investigated the expression and functional role of furin in Middle Eastern papillary thyroid carcinoma (PTC). Furin overexpression was observed in 44.6% of PTC cases and was associated with aggressive clinicopathological parameters and poor outcomes. Knockdown of FURIN suppressed tumor growth, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in BRAF mutant cells, while overexpression of FURIN reversed these effects in BRAF wild-type cells. FURIN inhibition showed a synergistic antitumor effect with anti-MEK inhibitor treatment.
MOLECULAR ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jessica Roelands, Peter J. K. Kuppen, Eiman I. Ahmed, Raghvendra Mall, Tariq Masoodi, Parul Singh, Gianni Monaco, Christophe Raynaud, Noel F. C. C. de Miranda, Luigi Ferraro, Tatiana C. Carneiro-Lobo, Najeeb Syed, Arun Rawat, Amany Awad, Julie Decock, William Mifsud, Lance D. Miller, Shimaa Sherif, Mahmoud G. Mohamed, Darawan Rinchai, Marc Van den Eynde, Rosalyn W. Sayaman, Elad Ziv, Francois Bertucci, Mahir Abdulla Petkar, Stephan Lorenz, Lisa Sara Mathew, Kun Wang, Selvasankar Murugesan, Damien Chaussabel, Alexander L. Vahrmeijer, Ena Wang, Anna Ceccarelli, Khalid A. Fakhro, Gabriele Zoppoli, Alberto Ballestrero, Rob A. E. M. Tollenaar, Francesco M. Marincola, Jerome Galon, Souhaila Al Khodor, Michele Ceccarelli, Wouter Hendrickx, Davide Bedognetti
Summary: The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, comprehensive genomic analyses were performed on fresh-frozen samples from 348 patients with primary colon cancer. The study revealed a gene expression signature called Immunologic Constant of Rejection that outperformed conventional prognostic molecular biomarkers. Additionally, a favorable outcome was associated with a microbiome signature driven by Ruminococcus bromii.
Article
Multidisciplinary Sciences
Abdul K. K. Siraj, Rong Bu, Sandeep Kumar Parvathareddy, Kaleem Iqbal, Saud Azam, Zeeshan Qadri, Maha Al-Rasheed, Wael Haqawi, Mark Diaz, Ingrid G. G. Victoria, Ismail A. A. Al-Badawi, Asma Tulbah, Fouad Al-Dayel, Dahish Ajarim, Khawla S. S. Al-Kuraya
Summary: By screening 918 breast cancer/ovarian cancer patients from Saudi Arabia, we identified six cases with pathogenic/likely pathogenic variants in the PALB2 gene, accounting for 0.65% of the entire cohort. Among these cases, two carried pathogenic variants and four carried likely pathogenic variants. All affected carriers had breast cancer, with a median age of diagnosis at 39.5 years, and only two cases had a documented family history of cancer.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Rong Bu, Abdul K. Siraj, Saud Azam, Kaleem Iqbal, Zeeshan Qadri, Maha Al-Rasheed, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya
Summary: This study identified a strong association between GALNT9 gene and rare inactivating variants in Middle Eastern population with Papillary thyroid carcinoma (PTC), and also found several other genes associated with PTC risk. The study highlights the potential role of GALNT9 and other genes in PTC predisposition and emphasizes the need for large collaborations and innovative approaches to understand the genetic heterogeneity of PTC predisposition.
Meeting Abstract
Oncology
Pratheeshkumar Poyil, Abdul K. Siraj, Divya Padmaja, Sandeep Kumar Parvathareddy, Roxanne Diaz, Saravanan Thangavel, Rafia Begum, Wael Haqawi, Khadija Alobaisi, Falah Hassan Al-Mohanna, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya
Meeting Abstract
Oncology
Saeeda Omer Ahmed, Abdul K. Siraj, Sandeep K. Parvathareddy, Kaleem Iqbal, Zeeshan Qadri, Maha Al-Rasheed, Sarah Siraj, Saravanan Thangavel, Roxanne Diaz, Allianah Benito, Ingrid F. Victoria, Khawla S. AlKuraya
Meeting Abstract
Oncology
Saeeda Omer Ahmed, Abdul K. Siraj, Sandeep K. Parvathareddy, Kaleem Iqbal, Zeeshan Qadri, Maha Al-Rasheed, Sarah Siraj, Saravanan Thangavel, Roxanne Diaz, Allianah Benito, Ingrid F. Victoria, Khawla S. AlKuraya
Meeting Abstract
Oncology
Rong Bu, Abdul K. Siraj, Tariq Masoodi, Sandeep Kumar Parvathareddy, Kaleem Iqbal, Allianah D. Benito, Sarah Siraj, Nabil Siraj, Maha Al Rasheed, Saeeda O. Ahmed, Wael AL-Haqaw, Maria Angelita Sabido, Mark Ranier Diaz, Padmanaban Annaiyappanaidu, Khawla S. Al-Kuraya
Meeting Abstract
Oncology
Rong Bu, Abdul K. Siraj, Tariq Masoodi, Sandeep Kumar Parvathareddy, Kaleem Iqbal, Allianah D. Benito, Sarah Siraj, Nabil Siraj, Maha Al Rasheed, Saeeda O. Ahmed, Wael AL-Haqaw, Maria Angelita Sabido, Mark Ranier Diaz, Padmanaban Annaiyappanaidu, Khawla S. Al-Kuraya
Meeting Abstract
Gastroenterology & Hepatology
Ajaz A. Bhat, Tariq Masoodi, Deepika Mishra, Mayank Singh, Sabah Nisar, Sheema Hashem, Ravi Chauhan, Anthony Akobeng, William Mifsud, Puneet Bagga, Ravinder Reddy, Punita Dhawan, Davide Bedognetti, Wael El-Rifai, Muzafar A. Macha, Mohammad Haris