James D. Brenton

Last updated
James D Brenton
Alma materUniversity College London, University of Cambridge
Scientific career
InstitutionsCancer Research UK Cambridge Institute, University of Cambridge Addenbrooke's Hospital
Website www.cruk.cam.ac.uk/research-groups/brenton-group

Professor James D Brenton is a clinician scientist and Senior Group Leader at the Cancer Research UK Cambridge Institute and Professor of Ovarian Cancer Medicine in the Department of Oncology, University of Cambridge. [1] He is an Honorary Consultant in Medical Oncology at Addenbrooke's Hospital, Cambridge University Hospitals, [2] Ovarian Cancer Domain Lead for the 100,000 Genomes Project by Genomics England, [3] and co-founder and Clinical Advisor to Inivata Ltd, a clinical cancer genomics company. [4]

Contents

Education and career

Dr Brenton studied Medicine at University College London, graduating in 1988, and trained in Medical Oncology at the Royal Marsden Hospital and Princess Margaret Cancer Centre, Toronto. [5] He completed his PhD at the Gurdon Institute before attaining a Senior Clinical Research Fellowship for his work at the MRC Cancer Unit. In 2007 he became a Senior Group Leader at the Cancer Research UK Cambridge Institute, leading the Functional Genomics of Ovarian Cancer laboratory.

Research

Brenton's research focuses on understanding the molecular complexity of ovarian cancer to improve treatment and patient outcome. [6] His team discovered a ubiquitous TP53 mutation in high grade serous ovarian cancer (HGSOC), [7] the most common form of ovarian cancer, which was adopted as a critical marker for diagnosing HGSOC by the World Health Organisation. [8] Brenton used this TP53 discovery to develop personalised circulating tumour DNA assays to measure treatment response in ovarian cancer. [9] [10]

In 2015, his team was the first to measure the tumour heterogeneity in a solid tumour and link this to cancer survival, finding that HGSOC was more deadly if it consisted of a patchwork of different groups of cells. [11] [12] [13] [14] [15]

In 2018, Brenton published the first national effort to investigate cancer evolution in HGSOC, discovering seven distinct genetic patterns that could predict disease behaviour in response to treatment. [16] [17] [18] [19] This led to the BriTROC-2 study, funded by Ovarian Cancer Action, to create new, personalised treatments for women with HGSOC. [20]

Related Research Articles

<span class="mw-page-title-main">Carcinoma</span> Malignancy that develops from epithelial cells

Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal or ectodermal germ layer during embryogenesis.

<span class="mw-page-title-main">Endometrial cancer</span> Uterine cancer that is located in tissues lining the uterus

Endometrial cancer is a cancer that arises from the endometrium. It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most often vaginal bleeding not associated with a menstrual period. Other symptoms include pain with urination, pain during sexual intercourse, or pelvic pain. Endometrial cancer occurs most commonly after menopause.

<span class="mw-page-title-main">Ovarian cancer</span> Cancer originating in or on the ovary

Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different cell types including epithelial cells, germ cells, and stromal cells. When these cells become abnormal, they have the ability to divide and form tumors. These cells can also invade or spread to other parts of the body. When this process begins, there may be no or only vague symptoms. Symptoms become more noticeable as the cancer progresses. These symptoms may include bloating, vaginal bleeding, pelvic pain, abdominal swelling, constipation, and loss of appetite, among others. Common areas to which the cancer may spread include the lining of the abdomen, lymph nodes, lungs, and liver.

<span class="mw-page-title-main">Li–Fraumeni syndrome</span> Autosomal dominant cancer syndrome

Li–Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary disorder that predisposes carriers to cancer development. It was named after two American physicians, Frederick Pei Li and Joseph F. Fraumeni Jr., who first recognized the syndrome after reviewing the medical records and death certificates of childhood rhabdomyosarcoma patients. The disease is also known as SBLA, for the Sarcoma, Breast, Leukemia, and Adrenal Gland cancers that it is known to cause.

<span class="mw-page-title-main">Ovarian clear-cell carcinoma</span> One of the subtypes of ovarian carcinoma

Ovarian clear-cell carcinoma, or clear-cell carcinoma of the ovary, also called ovarian clear-cell adenocarcinoma, is one of several subtypes of ovarian carcinoma – a subtype of epithelial ovarian cancer, in contrast to non-epithelial cancers. According to research, most ovarian cancers start at the epithelial layer which is the lining of the ovary. Within this epithelial group ovarian clear-cell carcinoma makes up 5–10%.

<span class="mw-page-title-main">Serous tumour</span> Medical condition

A serous tumour is a neoplasm that typically has papillary to solid formations of tumor cells with crowded nuclei, and which typically arises on the modified Müllerian-derived serous membranes that surround the ovaries in females. Such ovarian tumors are part of the surface epithelial-stromal tumour group of ovarian tumors. They are common neoplasms with a strong tendency to occur bilaterally, and they account for approximately a quarter of all ovarian tumors.

<span class="mw-page-title-main">Surface epithelial-stromal tumor</span> Medical condition

Surface epithelial-stromal tumors are a class of ovarian neoplasms that may be benign or malignant. Neoplasms in this group are thought to be derived from the ovarian surface epithelium or from ectopic endometrial or fallopian tube (tubal) tissue. Tumors of this type are also called ovarian adenocarcinoma. This group of tumors accounts for 90% to 95% of all cases of ovarian cancer; however is mainly only found in postmenopausal women with the exception of the United States where 7% of cases occur in women under the age of 40. Serum CA-125 is often elevated but is only 50% accurate so it is not a useful tumor marker to assess the progress of treatment. 75% of women with epithelial ovarian cancer are found within the advanced-stages; however younger patients are more likely to have better prognoses than older patients.

<span class="mw-page-title-main">Personalized medicine</span> Medical model that tailors medical practices to the individual patient

Personalized medicine, also referred to as precision medicine, is a medical model that separates people into different groups—with medical decisions, practices, interventions and/or products being tailored to the individual patient based on their predicted response or risk of disease. The terms personalized medicine, precision medicine, stratified medicine and P4 medicine are used interchangeably to describe this concept, though some authors and organizations differentiate between these expressions based on particular nuances. P4 is short for "predictive, preventive, personalized and participatory".

<span class="mw-page-title-main">Primary peritoneal carcinoma</span> Medical condition

Primary peritoneal cancer or carcinoma is also known as serous surface papillary carcinoma, primary peritoneal carcinoma, extra-ovarian serous carcinoma, primary serous papillary carcinoma, and psammomacarcinoma. It was historically classified under "carcinoma of unknown primary" (CUP). Primary peritoneal cancer is a cancer of the cells lining the peritoneum, or abdominal cavity. It usually affects women and is diagnosed after the age of 60; it very rarely affects men.

Gynecologic oncology is a specialized field of medicine that focuses on cancers of the female reproductive system, including ovarian cancer, uterine cancer, vaginal cancer, cervical cancer, and vulvar cancer. As specialists, they have extensive training in the diagnosis and treatment of these cancers.

<span class="mw-page-title-main">Fallopian tube cancer</span> Medical condition

Primary fallopian tube cancer (PFTC), also known as tubal cancer, is a malignant neoplasm that originates from the fallopian tube. Along with primary ovarian and peritoneal carcinomas, it is grouped under epithelial ovarian cancers; cancers of the ovary that originate from a fallopian tube precursor.

<span class="mw-page-title-main">Rucaparib</span> Chemical compound

Rucaparib, sold under the brand name Rubraca, is a PARP inhibitor used as an anti-cancer agent. Rucaparib is a first-in-class pharmaceutical drug targeting the DNA repair enzyme poly-ADP ribose polymerase-1 (PARP-1). It is taken by mouth.

A borderline tumor, sometimes called low malignant potential (LMP) tumor, is a distinct but yet heterogeneous group of tumors defined by their histopathology as atypical epithelial proliferation without stromal invasion. It generally refers to such tumors in the ovary but borderline tumors may rarely occur at other locations as well.

<span class="mw-page-title-main">Hereditary cancer syndrome</span> Inherited genetic condition that predisposes a person to cancer

A hereditary cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancer and may also cause early onset of these cancers. Hereditary cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors.

<span class="mw-page-title-main">High-grade serous carcinoma</span> Medical condition

High-grade serous carcinoma (HGSC) is a type of tumour that arises from the serous epithelial layer in the abdominopelvic cavity and is mainly found in the ovary. HGSCs make up the majority of ovarian cancer cases and have the lowest survival rates. HGSC is distinct from low-grade serous carcinoma (LGSC) which arises from ovarian tissue, is less aggressive and is present in stage I ovarian cancer where tumours are localised to the ovary.

Professor Carlos Caldas is a clinician scientist and Professor of Cancer Medicine at the University of Cambridge. He is the Chair of Cancer Medicine at the University of Cambridge, an Honorary Consultant Medical Oncologist at Addenbrooke's Hospital and Director of the Cambridge Breast Cancer Research Unit. He is a fellow of Robinson College, Cambridge and an Emeritus Senior Investigator at the National Institute for Health Research (NIHR).

Serena Nik-Zainal is a British-Malaysian clinician who is a consultant in clinical genetics and Cancer Research UK advanced clinician scientist at the University of Cambridge. She makes use of genomics for clinical applications. She was awarded the Crick Lecture by the Royal Society in 2021. Serena Nik-Zainal was also recognized as one of the 100 Influential Women in Oncology by OncoDaily.

Nitzan Rosenfeld is a professor of Cancer Diagnostics at the University of Cambridge. He is a Senior Group Leader at the Cancer Research UK Cambridge Institute and co-founder of Inivata, a clinical cancer genomics company.

<span class="mw-page-title-main">SEE-FIM Protocol</span> Pathology protocol to assess cancer risk

The SEE-FIM protocol is a pathology dissection protocol for Sectioning and Extensively Examining the Fimbria (SEE-FIM). This protocol is intended to provide for the optimal microscopic examination of the distal fallopian tube (fimbria) to identify either cancerous or precancerous conditions in this organ.

Florian Markowetz is the Professor of Computational Oncology at the University of Cambridge. He is a Senior Group Leader at the Cancer Research UK Cambridge Institute and Director and co-founder of Tailor Bio, a genomics company aiming to improve precision medicine for cancers with high levels of chromosomal instability.

References

  1. ↑ "Dr James Brenton". Cancer Research UK. 2016-07-26. Retrieved 2019-11-18.
  2. ↑ "Dr James Brenton | Cambridge University Hospitals". www.cuh.nhs.uk. Retrieved 2019-11-18.
  3. ↑ "Genomics England Announce Lead Researchers". Front Line Genomics. Retrieved 2019-11-18.
  4. ↑ "New Review of ctDNA Liquid Biopsies in Nature Reviews Cancer Co-Authored by Inivata CSO Nitzan Rosenfeld". Welcome to Inivata. 2017-02-24. Retrieved 2019-11-18.
  5. ↑ "Dr James Brenton". Cambridge Clinical Informatics. Retrieved 2019-11-18.
  6. ↑ "Research Gate".
  7. ↑ Ahmed, Ahmed Ashour; Etemadmoghadam, Dariush; Temple, Jillian; Lynch, Andy G; Riad, Mohamed; Sharma, Raghwa; Stewart, Colin; Fereday, Sian; Caldas, Carlos; deFazio, Anna; Bowtell, David (May 2010). "Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary". The Journal of Pathology. 221 (1): 49–56. doi:10.1002/path.2696. ISSN   0022-3417. PMC   3262968 . PMID   20229506.
  8. ↑ Duska, L. R.; Kohn, E. C. (2017-11-01). "The new classifications of ovarian, fallopian tube, and primary peritoneal cancer and their clinical implications". Annals of Oncology. 28 (suppl_8): viii8–viii12. doi:10.1093/annonc/mdx445. ISSN   0923-7534. PMC   6246280 . PMID   29232468.
  9. ↑ Parkinson, Christine A.; Gale, Davina; Piskorz, Anna M.; Biggs, Heather; Hodgkin, Charlotte; Addley, Helen; Freeman, Sue; Moyle, Penelope; Sala, Evis; Sayal, Karen; Hosking, Karen (2016-12-20). "Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study". PLOS Medicine. 13 (12): e1002198. doi: 10.1371/journal.pmed.1002198 . ISSN   1549-1676. PMC   5172526 . PMID   27997533.
  10. ↑ "Searching for a blood test to monitor ovarian cancer". Cancer Research UK - Science blog. 20 December 2016. Retrieved 2019-11-18.
  11. ↑ Schwarz, Roland F.; Ng, Charlotte K. Y.; Cooke, Susanna L.; Newman, Scott; Temple, Jillian; Piskorz, Anna M.; Gale, Davina; Sayal, Karen; Murtaza, Muhammed; Baldwin, Peter J.; Rosenfeld, Nitzan (2015-02-24). "Spatial and Temporal Heterogeneity in High-Grade Serous Ovarian Cancer: A Phylogenetic Analysis". PLOS Medicine. 12 (2): e1001789. doi: 10.1371/journal.pmed.1001789 . ISSN   1549-1676. PMC   4339382 . PMID   25710373.
  12. ↑ "'Patchwork' ovarian cancer more deadly". Cancer Research UK. 2015-02-24. Retrieved 2019-11-18.
  13. ↑ "Ovarian cancer more deadly if in 'patchwork' pattern | Cambridge University Hospitals". www.cuh.nhs.uk. Retrieved 2019-11-18.
  14. ↑ "Unpicking the genetic 'patchwork' in ovarian cancer". Cancer Research UK - Science blog. Retrieved 2019-11-18.
  15. ↑ "'Patchwork' ovarian cancer is most deadly". The Best Of Health. 4 March 2015. Retrieved 2019-11-18.
  16. ↑ Macintyre, Geoff; Goranova, Teodora E.; De Silva, Dilrini; Ennis, Darren; Piskorz, Anna M.; Eldridge, Matthew; Sie, Daoud; Lewsley, Liz-Anne; Hanif, Aishah; Wilson, Cheryl; Dowson, Suzanne (September 2018). "Copy number signatures and mutational processes in ovarian carcinoma". Nature Genetics. 50 (9): 1262–1270. doi:10.1038/s41588-018-0179-8. ISSN   1546-1718. PMC   6130818 . PMID   30104763.
  17. ↑ "Unravelling ovarian cancer genome complexity – NIHR Imperial Biomedical Research Centre" . Retrieved 2019-11-18.
  18. ↑ "Ovarian cancer genetics unravelled | Imperial News | Imperial College London" . Retrieved 2019-11-18.
  19. ↑ "Exciting new research could lead to personalised ovarian cancer treatments". Ovarian Cancer Action. Retrieved 2019-11-18.
  20. ↑ "BriTROC-2". Ovarian cancer Action. Retrieved 2019-11-18.
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