Tratamiento del cáncer de páncreas con ultrasonidos de baja intensidad: una revisión bibliográfica

El cáncer pancreático es una de las principales causas de muerte en Oncología, asociándose normalmente a un mal pronóstico y a una pobre respuesta al tratamiento. Actualmente, su diagnóstico y prevención resulta complicado, debido a la inexistencia de métodos y marcadores biológicos precisos y sensibles para esta enfermedad, y a que el paciente no refiere síntomas claros y específicos. En la mayoría de las ocasiones solo se diagnostica en estadios avanzados del tumor. A lo anterior, se suma un escaso arsenal terapéutico, que suele ir encaminado a paliar los síntomas de la enfermedad. La mayoría de las mutaciones que promueven la carcinogénesis pancreática no son tratables; y, además, el complejo carácter metabólico de las células en este tipo de tumor y el denso estroma que se forma alrededor del mismo impiden la entrada del fármaco y, por consiguiente, su efecto. Así, en nuestra línea de investigación (de tipo “proof of concept”) se presenta una alternativa terapéutica naciente para este tipo de patología mediante el uso de los llamados ultrasonidos de baja intensidad (LIUS, Low Intensity Ultrasounds), de manera totalmente novedosa, estudiando el efecto de dichos ultrasonidos a nivel celular y molecular e intentando extrapolar los resultados a la clínica en beneficio de los pacientes. Este trabajo consiste en una extensa revisión de la literatura sobre los aspectos clave de nuestra investigación: el cáncer de páncreas y sus aspectos clínicos y moleculares, por un lado, y los ultrasonidos, por otro. Como conclusión, se incluye una discusión que relaciona todo el contenido de la revisión teórica con nuestro trabajo y nuestras observaciones experimentales preliminares, así como el futuro de nuestro proyecto y los pasos a seguir en el desarrollo del mism

Ultrasounds in cancer therapy: A summary of their use and unexplored potential

8 páginas, 2 tablasUltrasounds (US) are a non-ionizing mechanical wave, with less adverse effects than conventional pharmacological or surgical treatments. Different biological effects are induced in tissues and cells by ultrasound actuation depending on acoustic parameters, such as the wave intensity, frequency and treatment dose. This non-ionizing radiation has considerable applications in biomedicine including surgery, medical imaging, physical therapy and cancer therapy. Depending on the wave intensity, US are applied as high-intensity ultrasounds (HIUS) and low-intensity pulsed ultrasounds (LIPUS), with different effects on cells and tissues. HIUS produce thermal and mechanical effects, resulting in a large localized temperature increase, leading to tissue ablation and even tumor necrosis. This can be achieved by focusing low intensity waves emitted from different electrically shifted transducers, known as high-intensity focused ultrasounds (HIFU). LIPUS have been used extensively as a therapeutic, surgical and diagnostic tool, with diverse biological effects observed in tissues and cultured cells. US represent a non-invasive treatment strategy that can be applied to selected areas of the body, with limited adverse effects. In fact, tumor ablation using HIFU has been used as a curative treatment in patients with an early-stage pancreatic tumor and is an effective palliative treatment in patients with advanced stage disease. However, the biological effects, dose standardization, benefit-risk ratio and safety are not fully understood. Thus, it is an emerging field that requires further research in order to reach its full potential.The authors would like to acknowledge the following funding related with the effects of ultrasounds on cancer cells and tissues: Spanish National Plan project RETOS DPI 2017-90147-R. Intramural call for new research projects for clinical researchers and emerging research groups. IRYCIS. (2018/0240). Ibero-American Network CYTED-DITECROD-218RT0545

Ultrasound Technology as a Novel Treatment Strategy in Pancreatic Cancer

Adenocarcinoma of the pancreas (PDAC) accounts for 2.4% of all cancers diagnosed and is the fourth leading cause of cancer death, with almost equal rates of incidence and mortality [1]. By 2030, pancreatic cancer is projected to be the second leading cause of cancer-related death [2], surpassing breast, prostate and colorectal cancer. The overall survival at 5 years of around 7.2% as the majority of patients present with advanced disease at diagnosis. Patients with localized disease are treated with surgery, with or without neoadjuvant chemotherapy/ radiotherapy, followed by adjuvant chemotherapy. The majority (around 80%) of patients are treated only with chemotherapy as they have an advanced disease. Patients are treated in the first line with gemcitabine-abraxane or Folfirinox and with Naliri plus 5FU in the second line. There have been few clinical advances in PDAC treatment over the last 20 years and chemotherapy is the only treatment option available for the majority of patients. These tumours are also resistant to many targeted therapies such as anti-EGFR therapy like cetuximab [3] due to the presence of a KRAS mutation in the majority of primary tumors. Personalized medicine strategies have not yet been established in pancreatic cancer as in other more common tumour types. Thus, novel anti-tumour strategies are an important clinical need in order to improve survival rates.AEI/FEDER, UE DPI 2017-90147-R.Intramural call for new research projects for clinical researchers and emerging research groups. IRYCIS. (2018/0240)Iberoamerican Network CYTED-DITECROD-218RT0545.Peer reviewe

Establishment of Pancreatic Cancer-Derived Tumor Organoids and Fibroblasts From Fresh Tissue.

Tumor organoids are three-dimensional (3D) ex vivo tumor models that recapitulate the biological key features of the original primary tumor tissues. Patient-derived tumor organoids have been used in translational cancer research and can be applied to assess treatment sensitivity and resistance, cell-cell interactions, and tumor cell interactions with the tumor microenvironment. Tumor organoids are complex culture systems that require advanced cell culture techniques and culture media with specific growth factor cocktails and a biological basement membrane that mimics the extracellular environment. The ability to establish primary tumor cultures highly depends on the tissue of origin, the cellularity, and the clinical features of the tumor, such as the tumor grade. Furthermore, tissue sample collection, material quality and quantity, as well as correct biobanking and storage are crucial elements of this procedure. The technical capabilities of the laboratory are also crucial factors to consider. Here, we report a validated SOP/protocol that is technically and economically feasible for the culture of ex vivo tumor organoids from fresh tissue samples of pancreatic adenocarcinoma origin, either from fresh primary resected patient donor tissue or patient-derived xenografts (PDX). The technique described herein can be performed in laboratories with basic tissue culture and mouse facilities and is tailored for wide application in the translational oncology field