Integrating the Tumor Microenvironment into Cancer Therapy
© 2020 by the authors.
Una visión integral del cáncer (I). Microambiente tumoral: estudio, clasificación y reprogramación
Resumen El grupo de enfermedades al que nos referimos como «cancer» comparte una estructura biologica conformada por un ecosistema complejo, donde se han alterado las relaciones intercelulares, los campos de informacion, el desarrollo y la funcion tisular. Mas alla de las alteraciones geneticas de la celula tumoral, la demostracion de un ecosistema alterado, con sus interconexiones a nivel sistemico, abre una nueva perspectiva de la biologia y del comportamiento del cancer. Diversas facetas del tumor, su morfologia, clasificacion, agresividad clinica, pronostico y respuesta al tratamiento aparecen ahora bajo una vision integral que ofrece un nuevo horizonte de estudio, investigacion y manej…
Abstract OT-13-06: Solti-1503 PROMETEO: Talimogene laherparepvec (T-VEC) + atezolizumab combination in early breast cancer
Abstract Background Residual disease (RD) after standard neoadjuvant chemotherapy (NAC) is composed of drug resistant cells and associates with increased risk of relapse, especially in triple negative, HER2-positive, and highly proliferative Luminal tumors. Immunotherapy combinations can induce of specific anti-tumor immune responses, such as those mediated by T-cells, and which might represent an additional strategy for the control or elimination of residual tumor cells. Preliminary results in melanoma showed that the combination of T-VEC with an anti PD-L1 or anti CTLA4 has greater efficacy than either therapy alone, without additional safety concerns beyond those expected for each agent.…
Una visión integral del cáncer (II). Campos de estudio y biomarcadores emergentes
Pathology and clinical oncology work hand in hand so that techniques and treatments, biomarkers and antibodies share the common goal of identifying integral new treatment regimens that are more effective and less aggressive. Evidence shows how tissue mechanics affect carcinogenesis and that tumor heterogeneity depends on metabolic stromal alteration and the Warburg effect of malignant cells, regulated directly by PD-1, becoming a target for immunotherapy. Proliferation and apoptosis depend on mitochondrial dysfunction in tumor cells, determining the grade of chemo/radio-resistance. The status of intestinal microbiota regulates immune response, tumor microenvironment structure and oncologic …
Immunometabolism Modulation in Therapy.
The study of cancer biology should be based around a comprehensive vision of the entire tumor ecosystem, considering the functional, bioenergetic and metabolic state of tumor cells and those of their microenvironment, and placing particular importance on immune system cells. Enhanced understanding of the molecular bases that give rise to alterations of pathways related to tumor development can open up new therapeutic intervention opportunities, such as metabolic regulation applied to immunotherapy. This review outlines the role of various oncometabolites and immunometabolites, such as TCA intermediates, in shaping pro/anti-inflammatory activity of immune cells such as MDSCs, T lymphocytes, …
Una visión integral del cáncer (III). Evaluación de nuevos biomarcadores y posibilidades de intervención
We propose a comprehensive approach to oncological disease, based on a systemic consideration of biology, health and disease. Our two previous review articles focused on tumour microenvironment and the discovery of new biomarkers; here we discuss the practical application of these principles to pathology, through the identification, evaluation and quantitative analysis of new prognostic and predictive factors (Immunoscore, TIME). We also consider the clinical use of promising, better tolerated treatments, such as immunotherapy. The integrative pathologist now has access to the latest improved oncology stratification tools designed to identify effective treatment strategies, based on the nat…
Metabolic classification and intervention opportunities for tumor energy dysfunction
A comprehensive view of cell metabolism provides a new vision of cancer, conceptualized as tissue with cellular-altered metabolism and energetic dysfunction, which can shed light on pathophysiological mechanisms. Cancer is now considered a heterogeneous ecosystem, formed by tumor cells and the microenvironment, which is molecularly, phenotypically, and metabolically reprogrammable. A wealth of evidence confirms metabolic reprogramming activity as the minimum common denominator of cancer, grouping together a wide variety of aberrations that can affect any of the different metabolic pathways involved in cell physiology. This forms the basis for a new proposed classification of cancer accordin…
The tumour microenvironment as an integrated framework to understand cancer biology
Cancer cells all share the feature of being immersed in a complex environment with altered cell-cell/cell-extracellular element communication, physicochemical information, and tissue functions. The so-called tumour microenvironment (TME) is becoming recognised as a key factor in the genesis, progression and treatment of cancer lesions. Beyond genetic mutations, the existence of a malignant microenvironment forms the basis for a new perspective in cancer biology where connections at the system level are fundamental. From this standpoint, different aspects of tumour lesions such as morphology, aggressiveness, prognosis and treatment response can be considered under an integrated vision, givin…
SOLTI-1503 PROMETEO TRIAL: combination of talimogene laherparepvec with atezolizumab in early breast cancer
New treatment strategies such as immune checkpoint inhibitors and oncolytic viruses are opening new possibilities in cancer therapy. Preliminary results in melanoma and other tumors showed that the combination of talimogene laherparepvec with an anti-PD-1/PD-L1 or anti-CTLA4 has greater efficacy than either therapy alone, without additional safety concerns beyond those expected for each agent. The presence of residual cancer after neoadjuvant chemotherapy in early breast cancer patients is an unmet medical need. SOLTI-1503 PROMETEO is a window of opportunity trial, which evaluates the combination of talimogene laherparepvec in combination with atezolizumab in women with operable HER2-negati…