Multi-omics characterization of squamous cell carcinoma of the head and neck by gaseous and liquid biopsy: diagnostic, prognostic and follow-up application. HN-OMICS

PMP22/00004
Year: 2022
Autonomous Communities: CATALONIA

Summary

Squamous Cell Carcinoma of the Head and Neck (HNSCC) is diagnosed in more than half a million patients a year worldwide, being the third tumour in developed countries and the sixth malignant tumour with the highest incidence worldwide. 60% of patients with HNSCC have an advanced stage of the disease at the time of diagnosis, with the survival of these patients at 5 years being 50%, making it a cancer with a high mortality. Currently, the main known risk factors for HNSCC include tobacco and alcohol use, and human papillomavirus infection. In a large number of cases, carcinoma develops from dysplastic lesions with the potential to evolve into malignancy

Surgical treatment of advanced tumors requires aggressive surgery with considerable functional sequelae. Different chemotherapy and radiotherapy schemes are currently used in this situation to avoid surgery. The main objective of conservative treatment is to achieve control rates comparable to those of radical treatment, preserving the functionality of the affected organ and the patient’s quality of life

However, the response to treatment is variable. Locoregional relapse occurs in 15-30% of patients with initial tumors and in more than 50% of patients with advanced tumors treated with radiotherapy or chemoradiotherapy. In these patients, survival decreases drastically, and they also suffer the morbidity of ineffective and highly aggressive treatment, and may require rescue treatment with surgery, which usually involves greater aggressiveness, with a higher rate of complications and sequelae, not to mention the high cost to the system.

A prediction of each patient and tumor profile to chemoradiotherapy would be of great value for the clinician to choose the best diagnostic and therapeutic approach. Thus, non-surgical strategies would only be offered to tumors classified as treatment-sensitive, while non-sensitive but resectable tumors would be targeted for entry surgery. The ultimate goal is to minimize morbidity and maximize survival of these aggressive tumors.

Coordinator and Institution

Principal Investigator
AVILÉS JURADO, FRANCISCO JAVIER
Institution
Objectives
  1. To characterize a molecular pattern based on metabolites and proteins associated with risk factors (tobacco use, alcohol consumption, and HPV infection) in a control group of patients without squamous cell carcinoma of the head and neck.
  2. To identify a specific molecular pattern associated with squamous cell carcinoma of the head and neck in noninvasive biological matrices (exhaled air, saliva) and tumor tissue in patients with risk factors (tobacco use, alcohol, and HPV infection) and proven squamous cell carcinoma of the head and neck.
  3. To determine the molecular pattern of patients treated with chemoradiotherapy according to their response to treatment.
  4. Identify changes in the metabolic profile that indicate the presence of tumor recurrence after treatment.
Impact

Above all, this project aims to advance and achieve the validation and/or clinical implementation of omics technologies as an instrumental basis for the deployment of personalized health in the NHS. This project has a clear focus on clinical transfer and the care of our patients

Knowledge of the behaviour of tumours and their expression of this behaviour in minimally invasive matrices will improve diagnosis and allow us to propose a more effective and individualised treatment. In addition, it will increase the chances of survival of affected patients and prevent them from suffering serious functional problems. This should allow for a better quality of life and better reintegration of individuals into everyday life.

There are new non-invasive methods that could become a simple, cost-effective and easy-to-use alternative to biopsy and follow-up monitoring. These methods allow for easy sampling to monitor disease status, without causing any pain or inconvenience to patients compared to tissue biopsy and disease monitoring in the clinical routine. In fact, the proposed non-invasive method is easy to integrate into the clinical routine and will maintain patients’ compliance during follow-up more effectively than more invasive biopsies.

We hope to provide valuable molecular information and useful biomarkers. Once the targets involved in radioresistance have been identified, the future of this project will be the development of new therapeutic options, with the social and economic impact that this highly prevalent and deadly disease would entail.

In short, this project will first serve to gain a new perspective not studied until now for head and neck cancer. Subsequently, it will serve to identify new prognostic markers in new matrices never before analyzed, which will result in a clear benefit for patients. Third, it may help reclassify treatments for these patients, if a pattern associated with resistance to radiation therapy is found. All this will also mean a better optimization of health expenditure in this disease and will save unnecessary suffering to certain groups of patients.

  1. Production of new knowledge: Our integrative analysis will allow the detection of potential new biomarkers for early diagnosis and response to treatment in the HNSCC. Therefore, at a clinical level, we will obtain a better knowledge about the behavior of these tumors than what is currently obtained with endoscopic exploration, radiological changes and metabolic functional tests. At the biological level, we will obtain information about the different expression layers of tumour biology and the relationship between them.
  2. Development of new research: One of the main strengths of this project is the comprehensive approach to the matrices evaluated, the techniques used to analyze them, and the integration of the data. Despite advances in diagnostic methodology and molecular biology, there is still a lack of early and/or non-invasive diagnostic methods. We aim to fill this gap by applying these novel methodologies to innovative sources of non-invasive samples such as exhaled air or saliva.
  3. Application of the results to improve treatments and clinical decision-making: The main ambition of the study is to transfer comprehensive knowledge of these tumors to current clinical practice. Thus, everything is designed to optimize: i) the early identification of possible lesions, ii) the detection of tumors that do not respond to QTRT regimens and that would benefit from other therapeutic options and iii) the identification of altered metabolic pathways that can be modulated.
  4. Production of information for administrative decision-making: Our approach would have a great impact on healthcare, being able to considerably reduce hospitalisation costs, thus optimising the use of healthcare resources and their viability, as we have previously quantified.
  5. Training of human resources: The training of the medical specialists who make up the project will be essential in the coming years. In addition, in parallel and equally important, the training of basic scientists in the new modalities of omics sciences, methods of obtaining, integrating and analyzing data will be fundamental to intertwine these two pillars of oncological diseases: clinical, translational and basic research.
  6. Improve quality of life or patient satisfaction: The focus of this project is on the patient and how we can avoid unnecessary treatments. The rescue treatments for these tumours (laryngectomy, glossectomy, mandibulectomy) are extremely aggressive, affecting processes such as breathing, swallowing or phonation, without forgetting the impact on the physical image. Personalized treatment will be crucial to guarantee the survival and quality of life of our patients.
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