Navita Somaiah

Navita Somaiah
Institute of Cancer Research

About

59
Publications
5,604
Reads
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887
Citations
Citations since 2016
56 Research Items
886 Citations
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
2016201720182019202020212022050100150200250
Introduction
Skills and Expertise

Publications

Publications (59)
Article
The PBRM1 subunit of the PBAF (SWI/SNF) chromatin remodeling complex is mutated in ∼40% of clear cell renal cancers. PBRM1 loss has been implicated in responses to immunotherapy in renal cancer, but the mechanism is unclear. DNA damage-induced inflammatory signaling is an important factor determining immunotherapy response. This response is kept in...
Article
Full-text available
Background Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and d...
Chapter
This section discusses the evidence of hypofractionation for breast cancer. It mainly focuses on the explanation for breast cancer responding to increase in fraction size despite a significant drop in total dose, whilst avoiding any confounding effect of treatment time. The findings of the recent FAST-Forward trial are addressed.
Article
Full-text available
Background This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients. Methods Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam...
Article
Full-text available
Recent clinical trials in breast and prostate cancer have established that fewer, larger daily doses (fractions) of radiotherapy are safe and effective, but these do not represent personalised dosing on a patient-by-patient basis. Understanding cell and molecular mechanisms determining fraction size sensitivity is essential to fully exploit this th...
Article
Full-text available
The field of immuno-oncology has expanded rapidly over the past decade, but key questions remain. How does tumour-immune interaction regulate disease progression? How can we prospectively identify patients who will benefit from immunotherapy? Identifying measurable features of the tumour immune-microenvironment which have prognostic or predictive v...
Preprint
Full-text available
This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients. Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for br...
Article
Full-text available
Purpose Hydrogen peroxide (H2O2) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiotherapy (RT). We report the first Phase I trial testing the safety and tolerability of int...
Article
Full-text available
Background We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial. Met...
Article
The RTGene study was focused on the development and validation of new transcriptional biomarkers for prediction of individual radiotherapy patient responses to ionizing radiation. In parallel, for validation purposes, this study incorporated conventional biomarkers of radiation exposure, including the dicentric assay. Peripheral blood samples were...
Article
Full-text available
Background: Bio-banked formalin-fixed paraffin-embedded (FFPE) tissues provide an excellent opportunity for translational genomic research. Historically matched blood has not always been collected as a source of germline DNA. This project aimed to establish if normal FFPE breast tissue could be used as an alternative to blood. Methods: Exome seq...
Article
Full-text available
For triage purposes following a nuclear accident, blood-based gene expression biomarkers can provide rapid dose estimates for a large number of individuals. Ionizing-radiation-responsive genes are regulated through the DNA damage-response pathway, which includes activation of multiple transcription factors. Modulators of this pathway could potentia...
Conference Paper
Full-text available
Introduction Late Adverse Effects (LAEs) following adjuvant radiotherapy (RT) are common sequelae in free flaps used for breast reconstruction. Intra-arterial delivery of gene therapy to an isolated vascular region permits localised, targeted genetic modulation of reconstructed tissue, avoiding potential off-target effects in microscopic residual d...
Article
98 Background: A uniform fractionation schedule is used to deliver external beam RT for localised prostate tumours Individualising fractionation according to tumour biology may improve outcomes. In addition recurrence rates after RT vary considerably and better prognostic markers are needed to guide treatment choices. This study aims to identify if...
Article
Full-text available
Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnos...
Article
Full-text available
Background External beam radiotherapy is delivered using a uniform fractionation schedule for localised prostate tumours, individualising fractionation according to tumour biology could improve outcomes. Additionally recurrence rates following radiotherapy vary considerably, better prognostic markers could improve treatment stratification. This stu...
Article
Improvements in cancer survival mean that long-term toxicities, which contribute to the morbidity of cancer survivorship, are being increasingly recognized. Late adverse effects (LAEs) in normal tissues after radiotherapy (RT) are characterized by vascular dysfunction and fibrosis causing volume loss and tissue contracture, for example, in the free...
Article
Full-text available
Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnos...
Article
Preoperative breast radiation therapy (RT) is not a new concept, but older studies failed to change practice. More recently, there has been interest in revisiting preoperative RT using modern techniques. This current perspective discusses the indications, summarises the published literature and then highlights current clinical trials, with particul...
Article
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that does not cross an intact blood-brain barrier. In the EMILIA trial of T-DM1 vs capecitabine/lapatinib for HER2 positive advanced breast cancer, all patients had baseline brain imaging, and 9/450 (2%) of patients with negative baseline imaging developed new brain disease during T-DM...
Article
Background: Therapeutic radiotherapy is an important treatment of pelvic cancers. Historically, low-fiber diets have been recommended despite a lack of evidence and potentially beneficial mechanisms of fiber.Objective: This randomized controlled trial compared low-, habitual-, and high-fiber diets for the prevention of gastrointestinal toxicity in...
Chapter
Many women diagnosed with early breast cancer will be cured and survive for many years after their initial diagnosis. Therefore it is important to take into account the risk of the development of new primary malignancies in such patients. Patients may be predisposed to develop new primary cancers as a result of genetic predisposition, environmental...
Article
Full-text available
Large breast size is associated with increased risk of late adverse effects after surgery and radiotherapy for early breast cancer. It is hypothesised that effects of radiotherapy on adipose tissue are responsible for some of the effects seen. In this study, the association of breast composition with late effects was investigated along with other b...
Article
Full-text available
Aim: To correlate residual double strand breaks (DSB) 24h after 4Gy test doses to skin in vivo and to lymphocytes in vitro with adverse effects of earlier breast radiotherapy (RT). Patients and methods: Patients given whole breast RT ⩾5years earlier were identified on the basis of moderate/marked or minimal/no adverse effects despite the absence...
Article
Full-text available
Background and purpose: FAST-Forward is a phase 3 clinical trial testing a 1-week course of whole breast radiotherapy against the UK standard 3-week regimen after primary surgery for early breast cancer. Two acute skin toxicity substudies were undertaken to test the safety of the test schedules with respect to early skin reactions. Material and m...
Article
Late normal tissue toxicity varies widely between patients and limits breast radiotherapy dose. Here we aimed to determine its relationship to DNA damage responses of fibroblast cultures from individual patients. Thirty-five breast cancer patients, with minimal or marked breast changes after breast-conserving therapy consented to receive a 4 Gy tes...
Chapter
As a general rule, cancers respond to the total dose more than to the size of daily fractions used to deliver it. This contrasts with the response of late-reacting, dose-limiting healthy tissues, which are sensitive both to the total dose and to the fraction size. The general rule has been challenged by randomized clinical trials conducted since th...
Article
Full-text available
Localised prostate cancer, in particular, intermediate risk disease, has varied survival outcomes that cannot be predicted accurately using current clinical risk factors. External beam radiotherapy (EBRT) is one of the standard curative treatment options for localised disease and its efficacy is related to wide ranging aspects of tumour biology. Hi...
Article
11116 Background: Critical opinions for the lack of success of DNA double-strand break (DSB) repair as a predictive marker of normal tissue radiosensitivity include the argument that in vitro cellular responses correlate poorly with in vivo responses due to the modifying influence of tissue environment. In this study, we test the hypothesis that a...

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Projects

Project (1)
Project
The overall aim of this project is to develop existing knowledge on transcriptional responses to ionising radiation into a useable radiation specific biomarker of exposure and response.