Richard James Cote | |
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Education | BS., Biology BA., Chemistry MD |
Alma mater | University of California, Irvine University of Chicago |
Occupation(s) | Pathologist, academic and author |
Medical career | |
Institutions | Washington University in St. Louis Barnes Jewish Hospital University of Miami University of Southern California |
Richard James Cote is a pathologist, academic and author. He is the Edward Mallinckrodt Professor and Chair of the Department of Pathology and Immunology at Washington University in St. Louis School of Medicine, and the Pathologist-in-Chief at Barnes Jewish Hospital. [1]
Cote's research focuses on the cellular and molecular pathways of tumor progression, metastasis, and therapy response, developing nanoscale technologies for cancer diagnostics, and leading clinical trials in breast, lung, and bladder cancer, resulting in multiple patents. [2] He has published research articles and four books including Immunomicroscopy: A Diagnostic Tool for the Surgical Pathologist and Modern Surgical Pathology. His contributions to the field led him to be listed as a top American doctor by US News , Newsweek Health and Castle Connolly among others. [3] Additionally, he is the recipient of the 2013 Distinguished Alumnus of the Year award from UCI's School of Physical Sciences, the 2015 Miami Chamber of Commerce Bio-Medical Healthcare Heroes Award, [4] and the 2016 Society for Personalized Nano-Medicine Excellence in Service Award. [5]
Cote is a Fellow of the Royal College of Pathologists, the American Board of Pathology, Royal Society of Medicine and the International Society for Urological Pathology, as well as a Senior Member of the National Academy of Inventors, [6] and an elected member of the Association of American Physicians. [7]
Cote earned a BA in Chemistry and a BS in Biology from the University of California, Irvine in 1976, followed by an MD from the University of Chicago in 1980. He completed a surgical internship at the University of Michigan (1980-1981), pursued a pathology residency at Cornell University (1985-1987), and held several fellowships at Memorial Sloan Kettering Cancer Center between 1981 and 1990, including a post-doctoral fellowship with Lloyd Old at MSKCC in tumor immunology. Concurrently, he served as a Research Associate at Memorial Sloan Kettering (1983-1985) and as a Clinical Instructor at Cornell University (1987-1990). [8]
Cote continued his academic career as an Assistant Professor in the Department of Pathology at the University of Southern California School of Medicine from 1990 to 1995. His appointment was later extended to the Department of Urology, when he became Associate Professor in 1995 and Professor in 1999. In 2009, he took on the role of Professor and Chair of the Department of Pathology at the Miller School of Medicine at the University of Miami, [9] before joining the Department of Pathology and Immunology at Washington University School of Medicine, where he has held the position as the Edward Mallinckrodt Professor and Chair of the Department of Pathology and Immunology since 2019. [1]
Cote assumed the role of an Associate Member at the University of Southern California Norris Comprehensive Cancer Center from 1991 to 1995, later becoming a Member until 2009. During this time, he also served as an Attending Pathologist and Director of the Laboratory of Immuno and Molecular Pathology. From 1997 to 2009, he directed the Genitourinary Cancer Program at Norris Cancer Center and led the USC Biomedical Nanoscience Initiative from 2005 to 2009. Subsequently, from 2009 to 2015, he directed the Genitourinary Cancer Program and chaired the Department of Pathology at the University of Miami Sylvester Comprehensive Cancer Center. He also served as Director of the Dr. John T. Macdonald Foundation Biomedical Nanotechnology Institute and held the Joseph R. Coulter Jr. Chair in the Department of Pathology until 2019, when he became Chair of the Department of Pathology and Immunology at the Washington University School of Medicine. [10]
Cote has founded technology-based companies including Impath, Clarient, Filtini, Sensitini, and Circulogix. [11] From 2009 to 2019, he served as Chief of Pathology at Jackson Memorial Hospital before transitioning to the role of Pathologist-in-Chief at Barnes-Jewish Hospital, where he also holds a position on the Board of Directors. [12]
Cote has contributed to the field of pathology by elucidating cellular and molecular pathways of tumor progression, metastasis, and therapy response. He has developed programs to explore metastatic cancer spread and circulating tumor cell (CTC) biology, and has led clinical trials in breast, lung, and bladder cancer, holding patents in cancer-related and nanoscale technologies. [2]
Cote has published books on cancer therapy and immunohistochemistry. He co-authored the second and third editions of the standard text Immunomicroscopy: A Diagnostic Tool for the Surgical Pathologist with Clive Roy Taylor, providing clinical coverage, along with methods and expert interpretation skills for diagnosing pathology through immunomicroscopic techniques. In a review for Mayo Clinic Proceedings , Peter M. Banks stated that it is an "outstanding book that serves both as a reference source for methodologic details and as a conceptual text for scientific principles and diagnostic applications." [13] Later, he collaborated with Noel Weidner, Saul Suster and Lawrence Weiss for evaluating surgical specimens, integrating clinical, gross, microscopic, immunohistochemical, and molecular genetic features in two editions of Modern Surgical Pathology, which was called "a thorough and definitive 2-volume textbook" by Atiya Mansoor. [14]
Cote co-edited two volumes in the "Current Cancer Research" book series: Circulating Tumor Cells: Advances in Basic Science and Clinical Applications with Ram Datar, and Advances in Liquid Biopsy Technologies with Evi Lianidou. About the first edition, academic Sudeep Gupta remarked, "This book is a contemporary and comprehensive collection of reviews on technologies for estimating CTC, their genomic and functional characterization and clinical applications." [15]
Cote has studied cancer detection and diagnosis throughout his career. In collaborative research, he developed guidelines to improve HER2 testing accuracy in invasive breast cancer, recommending standardized procedures and criteria to ensure reliable results for all cases. [16] He is one of the founders of the field of liquid biopsy for cancer detection and evaluation and published the first study on the US on disseminated tumor cells (DTC) focusing on patients with early stage breast cancer, [17] and followed this up with a study showing that such cells identify patients at increased risk for metastasis. [18] He later worked with Munro Neville and the Ludwig Institute to publish a study showing that identification of occult tumor cells in the lymph nodes of patients with early-stage breast cancer identify those with increased risk for metastasis. [19] His work also revealed breast cancer stem cell phenotype in bone marrow disseminated tumor cells of early breast cancer patients, suggesting implications for metastasis and underscoring the need for further molecular analysis. [20] Additionally, he introduced a parylene membrane microfilter device for quick and efficient capture and analysis of circulating tumor cells (CTCs) in human blood. [21]
In a paper published in the New England Journal of Medicine, Cote and colleagues identified nuclear p53 accumulation as an independent predictor of poor outcomes in bladder-confined transitional-cell carcinoma, [22] while also demonstrating genetic discrepancies between papillary and flat transitional cell carcinomas, indicating diverse pathways of tumor progression. [23] He further showed that microcantilevers can detect prostate-specific antigen (PSA) in various concentrations, suggesting their potential for diagnosing prostate cancer and other diseases. [24] Later, alongside Shan-Rong Shi and Clive Taylor, he reviewed the antigen retrieval technique in immunohistochemical staining, emphasizing the need for standardized protocols and optimal retrieval methods. [25]
Cote's work on cancer therapy has focused on improving cancer treatment methods. He evaluated long-term outcomes of radical cystectomy and pelvic lymph node dissection in invasive bladder cancer, revealing that tumor stage and lymph node status significantly impact recurrence-free survival, supporting aggressive surgical management for excellent long-term results. [26] In another joint research effort, he showed that adjuvant cisplatin-based chemotherapy after radical cystectomy improves survival in muscle-invasive bladder cancer patients. [27] In 2022, he conducted a similar study which found that cisplatin-based adjuvant chemotherapy significantly improves overall, locoregional recurrence-free, and metastasis-free survival in patients with muscle-invasive bladder cancer. [28]
Cote was a Principal Consultant to Chromavision, one of the first companies to use digital pathology in diagnostic applications, where he led the effort to use digital images to detect CTC and to quantify Her2 expression in breast cancer. In addition, he has worked with colleagues at Caltech to develop microscopic methods that are designed to produce all-in-focus digital images of histologic and cytologic preparations, important for AI applications. [29] He has gone on to describe the use of digital microscopy and AI to identify CTC. [30] Most recently, his team described the application of AI on the diagnostic histology of patients with early stage lung cancer to predict which patients will suffer metastasis. [31]
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues.
A Krukenberg tumor refers to a malignancy in the ovary that metastasized from a primary site, classically the gastrointestinal tract, although it can arise in other tissues such as the breast. Gastric adenocarcinoma, especially at the pylorus, is the most common source. Krukenberg tumors are often found in both ovaries, consistent with its metastatic nature.
A biopsy is a medical test commonly performed by a surgeon, an interventional radiologist, or an interventional cardiologist. The process involves the extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is then fixed, dehydrated, embedded, sectioned, stained and mounted before it is generally examined under a microscope by a pathologist; it may also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous or inflammatory conditions.
Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the tumor are identified as rhabdomyoblasts.
Cancer staging is the process of determining the extent to which a cancer has grown and spread. A number from I to IV is assigned, with I being an isolated cancer and IV being a cancer that has metastasized and spread from its origin. The stage generally takes into account the size of a tumor, whether it has invaded adjacent organs, how many regional (nearby) lymph nodes it has spread to, and whether it has appeared in more distant locations (metastasized).
Carcinoembryonic antigen (CEA) describes a set of highly-related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Consequently, CEA is usually present at very low levels in the blood of healthy adults. However, the serum levels are raised in some types of cancer, which means that it can be used as a tumor marker in clinical tests. Serum levels can also be elevated in heavy smokers.
Pseudomyxoma peritonei (PMP) is a clinical condition caused by cancerous cells that produce abundant mucin or gelatinous ascites. The tumors cause fibrosis of tissues and impede digestion or organ function, and if left untreated, the tumors and mucin they produce will fill the abdominal cavity. This will result in compression of organs and will destroy the function of the colon, small intestine, stomach, or other organs. Prognosis with treatment in many cases is optimistic, but the disease is lethal if untreated, with death occurring via cachexia, bowel obstruction, or other types of complications.
A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if discovered in early stages.
Invasive carcinoma of no special type, invasive breast carcinoma of no special type (IBC-NST), invasive ductal carcinoma (IDC), infiltrating ductal carcinoma (IDC) or invasive ductal carcinoma, not otherwise specified (NOS) is a disease. For international audiences this article will use "invasive carcinoma NST" because it is the preferred term of the World Health Organization (WHO).
Adjuvant therapy, also known as adjunct therapy, adjuvant care, or augmentation therapy, is a therapy that is given in addition to the primary or initial therapy to maximize its effectiveness. The surgeries and complex treatment regimens used in cancer therapy have led the term to be used mainly to describe adjuvant cancer treatments. An example of such adjuvant therapy is the additional treatment usually given after surgery where all detectable disease has been removed, but where there remains a statistical risk of relapse due to the presence of undetected disease. If known disease is left behind following surgery, then further treatment is not technically adjuvant.
The sentinel lymph node is the hypothetical first lymph node or group of nodes draining a cancer. In case of established cancerous dissemination it is postulated that the sentinel lymph nodes are the target organs primarily reached by metastasizing cancer cells from the tumor.
Papillary thyroid cancer is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases. It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck. It is often well-differentiated, slow-growing, and localized, although it can metastasize.
Signet ring cell carcinoma (SRCC) is a rare form of highly malignant adenocarcinoma that produces mucin. It is an epithelial malignancy characterized by the histologic appearance of signet ring cells.
A circulating tumor cell (CTC) is a cell that has shed into the vasculature or lymphatics from a primary tumor and is carried around the body in the blood circulation. CTCs can extravasate and become seeds for the subsequent growth of additional tumors (metastases) in distant organs, a mechanism that is responsible for the vast majority of cancer-related deaths. The detection and analysis of CTCs can assist early patient prognoses and determine appropriate tailored treatments. Currently, there is one FDA-approved method for CTC detection, CellSearch, which is used to diagnose breast, colorectal and prostate cancer.
In medicine, desmoplasia is the growth of fibrous connective tissue. It is also called a desmoplastic reaction to emphasize that it is secondary to an insult. Desmoplasia may occur around a neoplasm, causing dense fibrosis around the tumor, or scar tissue (adhesions) within the abdomen after abdominal surgery.
Bone metastasis, or osseous metastatic disease, is a category of cancer metastases that result from primary tumor invasions into bones. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing sarcoma are rare; the most common bone tumor is a metastasis. Bone metastases can be classified as osteolytic, osteoblastic, or both. Unlike hematologic malignancies which originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial tumors and form a solid mass inside the bone. Primary breast cancer patients are particularly vulnerable to develop bone metastases. Bone metastases, especially in a state of advanced disease, can cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.
A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. Ideally, such biomarkers can be assayed in non-invasively collected biofluids like blood or serum.
The host response to cancer therapy is defined as a physiological response of the non-malignant cells of the body to a specific cancer therapy. The response is therapy-specific, occurring independently of cancer type or stage.
Carcinocythemia, also known as carcinoma cell leukemia, is a condition in which cells from malignant tumours of non-hematopoietic origin are visible on the peripheral blood smear. It is an extremely rare condition, with 33 cases identified in the literature from 1960 to 2018. Carcinocythemia typically occurs secondary to infiltration of the bone marrow by metastatic cancer and carries a very poor prognosis.
Recurrent cancer is any form of cancer that has returned or recurred when a fraction of primary tumor cells evade the effects of treatment and survive in small spaces that are undetectable by diagnostic tests. The initial tumor may become the site of cancer’s return or it may spread to another part of the body. These surviving cells accumulate various genetic changes over time, eventually producing a new tumor cell. It can take up to weeks, months, or even years for cancer to return. Following surgery and/or chemotherapy or radiotherapy, certain tumor cells may persist and develop resistance to treatment and eventually develop into new tumors. Age, sex, cancer type, treatment duration, stage of advancement, grade of original tumor, and cancer-specific risk factors are some of the factors that determine the rate of cancer recurrence. If recurrent cancer has already moved to other body parts or has developed chemo-resistance then it may be more aggressive than original cancer. In general, the severity of cancer increases with a shorter duration of time between initial treatment and its return.