Article
Biochemistry & Molecular Biology
Ivo Gokmen, Ebru Tastekin, Nazan Demir, Erkan Ozcan, Fahri Akgul, Muhammed Bekir Hacioglu, Bulent Erdogan, Sernaz Topaloglu, Irfan Cicin
Summary: The aim of this study was to investigate the incidence, molecular patterns, and associations with clinical parameters of KRAS/NRAS and BRAF mutations in colorectal cancer. KRAS mutation was the most common, with KRAS G12D being the most common mutation pattern. BRAF(V600E) was the most common BRAF mutation. Furthermore, there were associations observed between these mutations and age, gender, and tumor localization.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Xiao-na Chang, Fu-mei Shang, Hong-yu Jiang, Chen Chen, Zhe-yan Zhao, Sheng-he Deng, Jun Fan, Xiao-chuan Dong, Ming Yang, Yan Li, Kai-lin Cai, Li Liu, Hong-li Liu, Xiu Nie
Summary: In Central China, the incidence of colorectal cancer is rising, with high mortality rates. The mutation frequency of KRAS/NRAS/BRAF genes in CRC patients is significant, with BRAF mutation being associated with prognosis.
CURRENT MEDICAL SCIENCE
(2021)
Article
Oncology
Yang Li, Jun Xiao, Tiancheng Zhang, Yanying Zheng, Hailin Jin
Summary: This study investigated the characteristics of KRAS, NRAS, and BRAF mutations and microsatellite instability (MSI) in early colorectal cancer (ECRC) patients. It found that KRAS mutation can serve as an independent prognostic factor for ECRC patients. However, postoperative chemotherapy may not benefit ECRC patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Hanna Elomaa, Maarit Ahtiainen, Sara A. Vayrynen, Shuji Ogino, Jonathan A. Nowak, Marjukka Friman, Olli Helminen, Erkki-Ville Wirta, Toni T. Seppala, Jan Bohm, Markus J. Makinen, Jukka-Pekka Mecklin, Teijo Kuopio, Juha P. Vayrynen
Summary: This study evaluated the prognostic significance of tumour cell-T cell co-localisation and T cell densities in colorectal cancer patients. The findings showed that high T cell proximity score was associated with longer cancer-specific survival, indicating the potential of spatial measurement of T cell infiltrates as a novel, robust tumour-immune biomarker.
BRITISH JOURNAL OF CANCER
(2022)
Article
Medicine, General & Internal
Shen-Yi Lian, Lu-Xin Tan, Xin-Zhi Liu, Lu-Jing Yang, Ning-Ning Li, Qing Feng, Ping Wang, Yue Wang, Dong-Bo Qiao, Li-Xin Zhou, Ting-Ting Sun, Lin Wang, Ai-Wen Wu, Zhong-Wu Li
Summary: This study assessed the clinicopathological features and prognostic values of KRAS, NRAS, BRAF, and DNA mismatch repair status in colorectal cancer (CRC) in developing countries. The mutation frequencies of KRAS, NRAS, and BRAF were 41.7%, 1.6%, and 3.8%, respectively. KRAS mutations and deficient mismatch repair (dMMR) status were associated with aggressive biological behaviors and poor differentiation, while BRAF (V600E) mutations were associated with well-differentiated tumors. The dMMR status predicted longer overall survival in all CRC patients.
Article
Oncology
Hussein Akil, Mercedes Quintana, Jeremy H. Raymond, Tommy Billoux, Valentin Benboubker, Sophie Besse, Philippe Auzeloux, Veronique Delmas, Valerie Petit, Lionel Larue, Michel D'Incan, Francoise Degoul, Jacques Rouanet
Summary: Targeted radionuclide therapy (TRT) combined with MAPK/ERK inhibitors shows additive efficiency in BRAF and NRAS mutant melanoma cells. TRT has a significant therapeutic effect on NRAS(Q61K) mutated melanoma and reduces metastasis capacity.
Article
Medicine, General & Internal
Costel Stelian Brinzan, Mariana Aschie, Georgeta Camelia Cozaru, Mariana Deacu, Eugen Dumitru, Ionut Burlacu, Anca Mitroi
Summary: In this study, the mutation frequencies of genes in Romanian colorectal cancer patients were analyzed and compared with clinicopathological variables. The results showed correlations between these mutations and distant metastasis at diagnosis, MSI-H, proximal colon location, and well/moderately differentiated tumors. The findings of this study are generally consistent with data from other populations.
Article
Biochemistry & Molecular Biology
Vlad-Adrian Afrasanie, Mihai-Vasile Marinca, Bogdan Gafton, Teodora Alexa-Stratulat, Alexandra Rusu, Eliza-Maria Froicu, Daniel Sur, Cristian Virgil Lungulescu, Larisa Popovici, Andrei-Vlad Lefter, Irina Afrasanie, Anca-Viorica Ivanov, Lucian Miron, Cristina Rusu
Summary: In this study, the frequency, distribution, coexistence, and clinicopathological and molecular correlations of RAS, BRAF, PIK3CA, and TP53 mutations were investigated in 104 patients with metastatic colorectal cancer from Northeastern Romania. TP53 was the most frequently mutated gene (73.1%), followed by KRAS (45.2%) and PIK3CA (6.7%). The study provides novel insights into genetic variations specific to the population from Northeastern Romania and enables the development of genetic profiles in a developing country with limited access to specialized genetic tests.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Hiroyuki Takeda, Yu Sunakawa
Summary: BRAF mutations are an important poor prognostic factor in mCRC, but greater understanding of patient characteristics through genomic classification allows for more ideal treatment strategies.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Ahmad Machmouchi, Laudy Chehade, Sally Temraz, Ali Shamseddine
Summary: Targeted monoclonal antibody therapy against EGFR is a leading treatment for mCRC. However, resistance due to KRAS and BRAF mutations has emerged. Cells with these mutations overexpress GLUT1 and SVCT2, leading to intracellular vitamin C transport and cell death. High dose vitamin C shows promise in overcoming EGFR resistance in mCRC with wild KRAS mutation and in patients with KRAS and BRAF mutations, but more clinical trials are needed.
Review
Oncology
Junjia Liu, Hao Xie
Summary: This review explores the characteristics, clinical relevance, and treatment possibilities of BRAF non-V600 mutations in colorectal cancer, filling in existing knowledge gaps. Understanding the intricacies of these mutations can help healthcare professionals and researchers develop personalized treatment strategies to improve patient care.
Article
Genetics & Heredity
Peter W. Eide, Seyed H. Moosavi, Ina A. Eilertsen, Tuva H. Brunsell, Jonas Langerud, Kaja C. G. Berg, Bard I. Rosok, Bjorn A. Bjornbeth, Arild Nesbakken, Ragnhild A. Lothe, Anita Sveen
Summary: Gene expression-based subtypes of colorectal cancer have clinical significance, but the representativeness of primary tumors and consensus molecular subtypes (CMS) for metastatic cancers remains unclear. Metastases exhibit decreased CMS1/CMS3 signals and increased CMS4 signals, influenced by the microenvironment. The majority of classified metastases are CMS2 or CMS4, with subtype switching and inter-metastatic CMS heterogeneity being common.
NPJ GENOMIC MEDICINE
(2021)
Article
Multidisciplinary Sciences
Kristiaan J. Lenos, Sander Bach, Leandro Ferreira Moreno, Sanne ten Hoorn, Nina R. Sluiter, Sanne Bootsma, Felipe A. Vieira Braga, Lisanne E. Nijman, Tom van den Bosch, Daniel M. Miedema, Erik van Dijk, Bauke Ylstra, Ruth Kulicke, Fred P. Davis, Nicolas Stransky, Gromoslaw A. Smolen, Robert R. J. Coebergh van den Braak, Jan N. M. IJzermans, John W. M. Martens, Sally Hallam, Andrew D. Beggs, Geert J. P. L. Kops, Nico Lansu, Vivian P. Bastiaenen, Charlotte E. L. Klaver, Maria C. Lecca, Khalid El Makrini, Clara C. Elbers, Mark P. G. Dings, Carel J. M. van Noesel, Onno Kranenburg, Jan Paul Medema, Jan Koster, Lianne Koens, Cornelis J. A. Punt, Pieter J. Tanis, Ignace H. de Hingh, Maarten F. Bijlsma, Jurriaan B. Tuynman, Louis Vermeulen
Summary: A significant proportion of colorectal cancer patients develop peritoneal metastases, which are associated with poor disease outcome. This study characterizes peritoneal metastases from 52 patients and identifies a distinct molecular subtype. The researchers also discover the key role of the structural protein Moesin in peritoneal dissemination and confirm that polyclonal metastatic seeding underlies these lesions.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Lisa Dinter, Paula C. Karitzky, Alexander Schulz, Alexander A. Wurm, Marie-Christin Mehnert, Mildred Sergon, Antje Tunger, Mathias Lesche, Rebekka Wehner, Anja Mueller, Theresa Kaeubler, Heike Niessner, Andreas Dahl, Stefan Beissert, Marc Schmitz, Friedegund Meier, Barbara Seliger, Dana Westphal
Summary: This study investigated the combined effects of MEK inhibitors (MEKi) and BRAF inhibitors (BRAFi) on sensitive NRAS-mutant melanoma cells, including their ability to inhibit proliferation, induce apoptosis, and alter the expression of immune modulatory molecules. The study found that BRAFi significantly enhanced the antiproliferative and proapoptotic activity of MEKi, and upregulated the expression of immune relevant molecules in melanoma cells.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Medicine, General & Internal
Aleksandra Bozyk, Pawel Krawczyk, Katarzyna Reszka, Kinga Krukowska, Agnieszka Kolak, Slawomir Mandziuk, Kamila Wojas-Krawczyk, Rodryg Ramlau, Janusz Milanowski
Summary: This study found that mutations in the KRAS, NRAS and BRAF genes are not random and depend on the localization of colorectal cancer tumors. The mutation detection rate was significantly higher in women than in men, and tumors in the rectum and sigmoid colon were the most commonly observed in all patients.
ARCHIVES OF MEDICAL SCIENCE
(2022)
Review
Oncology
Neelima Vidula, Leif W. Ellisen, Aditya Bardia
Summary: Metastatic triple-negative breast cancer is being subtyped based on advances in genomics and molecular profiling, guiding the development of targeted therapies. New agents such as AKT inhibitors, checkpoint inhibitors, and PARP inhibitors are crucial for improving the treatment landscape for TNBC patients.
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
(2021)
Article
Oncology
Neelima Vidula, Andrzej Niemierko, Giuliana Malvarosa, Megan Yuen, Jochen Lennerz, A. John Iafrate, Seth A. Wander, Laura Spring, Dejan Juric, Steven Isakoff, Jerry Younger, Beverly Moy, Leif W. Ellisen, Aditya Bardia
Summary: Plasma-based genotyping can identify high rates of actionable mutations, leading to significant application of matched therapy and improved overall survival in patients with metastatic breast cancer.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Jing Xu, Tanya E. Keenan, Beth Overmoyer, Nadine M. Tung, Rebecca S. Gelman, Karleen Habin, Judy E. Garber, Leif W. Ellisen, Eric P. Winer, Paul E. Goss, Beow Y. Yeap, Bruce A. Chabner, Steven J. Isakoff
Summary: The study evaluated the efficacy and safety of the PARP inhibitors veliparib and temozolomide in metastatic breast cancer patients with or without germline BRCA1/2 mutations. While the primary endpoint was not met in unselected or BRCA-associated breast cancer, the combination showed clinical activity in platinum-naive BRCA-associated metastatic breast cancer with manageable toxicity at lower doses than the single-agent active dose. This regimen was further evaluated in a subsequent study.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Article
Oncology
Siang-Boon Koh, Kenneth Ross, Steven J. Isakoff, Nsan Melkonjan, Lei He, Karina J. Matissek, Andrew Schultz, Erica L. Mayer, Tiffany A. Traina, Lisa A. Carey, Hope S. Rugo, Minetta C. Liu, Vered Stearns, Adam Langenbucher, Srinivas Vinod Saladi, Sridhar Ramaswamy, Michael S. Lawrence, Leif W. Ellisen
Summary: This study identifies high levels of RASAL2 as predictors of chemotherapy response and long-term outcomes in TNBC. RASAL2 rewires MAPK feedback and cross-talk to confer resistance to MEK1/2 and EGFR inhibitors while also indicating sensitivity to these inhibitors.
CLINICAL CANCER RESEARCH
(2021)
Meeting Abstract
Oncology
Neelima Vidula, Erica Blouch, Nora K. Horick, Erin Basile, Senthil Damodaran, Minetta C. Liu, Ami N. Shah, Alvaro Moreno-Aspitia, Hope S. Rugo, Leif Ellisen, Aditya Bardi
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Lindsey Mortensen, Zehra Ordulu, Ibiayi Dagogo-Jack, Veerle Bossuyt, Loren Winters, Alphonse Taghian, Barbara L. Smith, Leif W. Ellisen, Lesli A. Kiedrowski, Jochen K. Lennerz, Aditya Bardia, Laura M. Spring
Summary: Enhanced understanding of the molecular events underlying oncogenesis has led to the development of tumoragnostic treatment strategies that target a tumor's genomic profile regardless of its anatomic site of origin. One classic example is the ETV6-NTRK3 gene fusion, which activates the TRK protein, leading to increased cell survival, growth, and proliferation.
Article
Oncology
James T. Coates, Sheng Sun, Ignaty Leshchiner, Nayana Thimmiah, Elizabeth E. Martin, Daniel McLoughlin, Brian P. Danysh, Kara Slowik, Raquel A. Jacobs, Kahn Rhrissorrakrai, Filippo Utro, Chaya Levovitz, Elyssa Denault, Charlotte S. Walmsley, Avinash Kambadakone, James R. Stone, Steven J. Isakoff, Laxmi Parida, Dejan Juric, Gad Getz, Aditya Bardia, Leif W. Ellisen
Summary: This study identified mechanisms of resistance to the antibody-drug conjugate (ADC) SG in different metastatic subclones of an individual patient, revealing genomic alterations in both antibody and drug payload targets. Experiments also demonstrated that a TROP2 gene mutation can confer resistance to SG.
Article
Oncology
Siang-Boon Koh, Brian N. Dontchos, Veerle Bossuyt, Christine Edmonds, Simona Cristea, Nsan Melkonjan, Lindsey Mortensen, Annie Ma, Kassidy Beyerlin, Elyssa Denault, Elizabeth Niehoff, Taghreed Hirz, David B. Sykes, Franziska Michor, Michelle Specht, Constance Lehman, Leif W. Ellisen, Laura M. Spring
Summary: Systematic collection of fresh tissues for research during diagnostic breast biopsy is safe, feasible, and efficient, providing a high-yield mechanism for diverse interdisciplinary research. The study demonstrated high diagnostic concordance between research and clinical specimens, consistent cell recovery, and potential clinical relevance in analyzing HER2 levels and immune microenvironment diversity.
NPJ PRECISION ONCOLOGY
(2021)
Editorial Material
Oncology
Siang-Boon Koh, Leif W. Ellisen
Summary: Zhang et al. conducted extensive single-cell immune compartment analyses of pre- and post-therapy triple-negative breast cancer and revealed potential mechanisms of T cell activation and patterns of immune evolution, which may inform future biomarkers of response and clinical benefit.
Review
Oncology
Rachel Occhiogrosso Abelman, Bogang Wu, Laura M. Spring, Leif W. Ellisen, Aditya Bardia
Summary: Antibody-drug conjugates (ADCs) are a promising class of therapies that deliver targeted treatment with fewer side effects. Despite their success, resistance to ADCs in breast cancer and other malignancies remains a challenge. This paper reviews the literature on the mechanisms of resistance to ADCs and discusses potential strategies to overcome them.
Article
Oncology
Neelima Vidula, Andrzej Niemierko, Katherine Hesler, Lianne Ryan, Beverly Moy, Steven Isakoff, Leif Ellisen, Dejan Juric, Aditya Bardia
Summary: We compared the cell-free DNA (cfDNA) results at the time of diagnosis of metastatic breast cancer (MBC) in patients who developed brain metastases (BM) with those who did not, in order to identify genomic predictors of BM. Among patients who underwent cfDNA testing at MBC diagnosis using Guardant360 (R) technology, we found that 21% of them developed BM. Comparing BM patients with non-BM patients, we observed a higher prevalence of specific gene mutations such as BRCA2, APC, CDKN2A, and SMAD4 in the former group. This genomic pattern had a high negative predictive value (85%) and specificity (93%) in excluding BM development.
Meeting Abstract
Oncology
Anosheh Afghahi, Sydney Marsh, Alyse Winchester, Dexiang Gao, Hannah Parris, Lisen Axell, Leif W. Ellisen, Erin Wysong Hofstatter, Allison W. Kurian, Marie Wood, Dana Zakalik, Carol-Ann Mullin, Jennifer Lee Caswell-Jin, Virginia F. Borges, Nadine M. Tung
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Meeting Abstract
Oncology
L. M. Spring, H. Han, E. Hamilton, H. Irie, C. A. Santa-Maria, J. Reeves, P. Pan, M. Shan, Y. Tang, J. R. Graham, S. Hazard, L. W. Ellisen, S. J. Isakoff
Article
Oncology
Kassidy Beyerlin, Rachel Jimenez, Mark Zangardi, Geoffrey G. Fell, Christine Edmonds, Andrew Johnson, Veerle Bossuyt, Michelle Specht, Therese M. Mulvey, Beverly Moy, Leif W. Ellisen, Steven J. Isakoff, Aditya Bardia, Laura M. Spring
Summary: The tolerability of adjuvant capecitabine for TNBC patients with residual disease in the United States is poor compared to the CREATE-X cohort. Administering adjuvant capecitabine in the US population poses challenges due to differences in tolerability, and further research is needed to understand its efficacy.
JOURNAL OF ONCOLOGY PHARMACY PRACTICE
(2021)
Meeting Abstract
Oncology
Laura M. Spring, Sara M. Tolaney, Neelam Desai, Amy Comander, Therese Mulvey, Ian E. Krop, Eric P. Winer, Elizabeth A. Mittendorf, Leif W. Ellisen, Aditya Bardia