Author
Wells A. Messersmith
Other affiliations: Georgetown University, Johns Hopkins University, Brigham and Women's Hospital ...read more
Bio: Wells A. Messersmith is an academic researcher from University of Colorado Boulder. The author has contributed to research in topics: Cancer & Colorectal cancer. The author has an hindex of 55, co-authored 295 publications receiving 12488 citations. Previous affiliations of Wells A. Messersmith include Georgetown University & Johns Hopkins University.
Topics: Cancer, Colorectal cancer, Gemcitabine, Irinotecan, Pancreatic cancer
Papers published on a yearly basis
Papers
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TL;DR: This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease and considers treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences.
Abstract: Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)-dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.
1,167 citations
TL;DR: This Review will discuss specific PDTX disease examples illustrating an overview of the opportunities and limitations of these models in cancer drug development, and describe concepts regarding predictive biomarker development and future applications.
Abstract: Progress in oncology drug development has been hampered by a lack of preclinical models that reliably predict clinical activity of novel compounds in cancer patients. In an effort to address these shortcomings, there has been a recent increase in the use of patient-derived tumour xenografts (PDTX) engrafted into immune-compromised rodents such as athymic nude or NOD/SCID mice for preclinical modelling. Numerous tumour-specific PDTX models have been established and, importantly, they are biologically stable when passaged in mice in terms of global gene-expression patterns, mutational status, metastatic potential, drug responsiveness and tumour architecture. These characteristics might provide significant improvements over standard cell-line xenograft models. This Review will discuss specific PDTX disease examples illustrating an overview of the opportunities and limitations of these models in cancer drug development, and describe concepts regarding predictive biomarker development and future applications.
1,093 citations
Northwestern University1, University of California, San Francisco2, University of Michigan3, University of California, San Diego4, City of Hope National Medical Center5, Vanderbilt University6, Seattle Cancer Care Alliance7, Fox Chase Cancer Center8, University of Wisconsin-Madison9, Mayo Clinic10, Yale University11, University of South Florida12, Washington University in St. Louis13, University of Alabama at Birmingham14, Stanford University15, Case Western Reserve University16, University of Colorado Boulder17, Harvard University18, Roswell Park Cancer Institute19, Memorial Sloan Kettering Cancer Center20, University of Utah21, University of Tennessee Health Science Center22, University of Texas MD Anderson Cancer Center23, Johns Hopkins University24, Duke University25, Ohio State University26
TL;DR: The NCCN Clinical Practice Guidelines in Oncology for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer.
Abstract: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Rectal Cancer address diagnosis, staging, surgical management, perioperative treatment, management of recurrent and metastatic disease, disease surveillance, and survivorship in patients with rectal cancer This portion of the guidelines focuses on the management of localized disease, which involves careful patient selection for curative-intent treatment options that sequence multimodality therapy usually comprised of chemotherapy, radiation, and surgical resection
655 citations
Northwestern University1, University of California, San Francisco2, University of Michigan3, University of California, San Diego4, City of Hope National Medical Center5, Vanderbilt University6, Seattle Cancer Care Alliance7, Fox Chase Cancer Center8, University of Wisconsin-Madison9, University of Utah10, Mayo Clinic11, Yale Cancer Center12, University of South Florida13, Washington University in St. Louis14, University of Alabama at Birmingham15, Stanford University16, Case Western Reserve University17, University of Colorado Boulder18, Brigham and Women's Hospital19, Ohio State University20, Roswell Park Cancer Institute21, Memorial Sloan Kettering Cancer Center22, University of Tennessee Health Science Center23, University of Texas MD Anderson Cancer Center24, Johns Hopkins University25, Duke University26, National Comprehensive Cancer Network27
TL;DR: The NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib are summarized.
Abstract: The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib.
653 citations
Northwestern University1, University of California, San Francisco2, University of Michigan3, City of Hope National Medical Center4, Vanderbilt University5, Seattle Cancer Care Alliance6, Fox Chase Cancer Center7, University of Wisconsin-Madison8, University of Texas Southwestern Medical Center9, University of Utah10, University of Nebraska Medical Center11, University of Alabama at Birmingham12, University of California, Los Angeles13, University of South Florida14, Mayo Clinic15, Washington University in St. Louis16, Yale Cancer Center17, Stanford University18, Case Western Reserve University19, University of Colorado Boulder20, Brigham and Women's Hospital21, Ohio State University22, Roswell Park Cancer Institute23, University of Texas MD Anderson Cancer Center24, Harvard University25, University of California, San Diego26, Memorial Sloan Kettering Cancer Center27, University of Pennsylvania28, University of Tennessee29, Johns Hopkins University30, Duke University31, National Comprehensive Cancer Network32
TL;DR: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section as discussed by the authors.
Abstract: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.
589 citations
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TL;DR: It is found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations, which defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors.
Abstract: There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, we searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for approximately 10(6) single-nucleotide polymorphisms. We found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. Our data indicate that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis.
3,721 citations
TL;DR: This Perspective has organized known cancer-associated metabolic changes into six hallmarks: deregulated uptake of glucose and amino acids, use of opportunistic modes of nutrient acquisition, useof glycolysis/TCA cycle intermediates for biosynthesis and NADPH production, increased demand for nitrogen, alterations in metabolite-driven gene regulation, and metabolic interactions with the microenvironment.
3,565 citations
Journal Article•
2,777 citations
Harvard University1, Sarah Cannon Research Institute2, University of California, San Francisco3, University of Colorado Denver4, University of Sydney5, Vanderbilt University6, University of Pennsylvania7, University of Melbourne8, University of South Florida9, University of Texas MD Anderson Cancer Center10, GlaxoSmithKline11
TL;DR: Dabrafenib and trametinib were safely combined at full monotherapy doses, and the rate of pyrexia was increased with combination therapy, whereas the rates of proliferative skin lesions was nonsignificantly reduced.
Abstract: Dose-limiting toxic effects were infrequently observed in patients receiving combination therapy with 150 mg of da braf e nib and 2 mg of tra me ti nib (combination 150/2). Cutaneous squamous-cell carcinoma was seen in 7% of patients receiving combination 150/2 and in 19% receiving monotherapy (P = 0.09), whereas pyrexia was more common in the combination 150/2 group than in the monotherapy group (71% vs. 26%). Median progression-free survival in the combination 150/2 group was 9.4 months, as compared with 5.8 months in the monotherapy group (hazard ratio for progression or death, 0.39; 95% confidence interval, 0.25 to 0.62; P<0.001). The rate of complete or partial response with combination 150/2 therapy was 76%, as compared with 54% with monotherapy (P = 0.03). Conclusions Da braf e nib and tra me ti nib were safely combined at full monotherapy doses. The rate of pyrexia was increased with combination therapy, whereas the rate of proliferative skin lesions was nonsignificantly reduced. Progression-free survival was significantly improved. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT01072175.)
2,457 citations