Development of a three-dimensional culture platform based on tumor cells derived from patients for the establishment of a model of personalized selection of drugs

Abstract

The treatment of cancer with chemotherapy is an expensive approach and the patient may suffer from side effects of a treatment that, after months, proves to be ineffective. The reason is each patient is unique with a unique genetic profile, which leads to different responses to the reference treatments. The practice of personalized oncology is dedicated to finding the most appropriate treatment for each patient individually. Predicting the response to a particular treatment based on patient genome data or tumor point mutations opened up new avenues for the oncologist to decide on the best treatment. However, these predictions do not necessarily confirm the efficacy of the therapy as well as being insufficient to indicate an effective option in advanced cancer patients who have failed in first, second and third line treatments. In this context, functional assays using patient-derived tumor organoids (PDOs) emerge as a potential individualized drug-selection platform in synergy with pharmacogenomic assays. PDOs are obtained by culture of tumor cells isolated from biopsy tissue or resection in three-dimensional (3D) systems that are able to recapitulate the characteristics of the patient's original tumor. Therefore, the response of the PDOs to the drugs tested may allow the prior deduction of how the patient will respond to the treatments. The objective of the present project is to develop a platform for the culture of PDOs of pancreatic, colorectal and lung tumors. For this, we will select an efficient method of processing tumor tissue samples through different techniques of dissociation and isolation of tumor cells; establish adequate conditions for 3D culture of PDOs using culture media and supplements specific for each type of tumor; and evaluate the applicability of the models generated by testing reference drugs. At the end of the phase 1 PIPE project, we hope to generate PDOs (minimum feasible product) for each type of tumor that will be validated in phase 2. Once the models are validated, the company will act in the provision of a personalized selection of drugs for patients with pancreatic, colorectal, and lung cancer using functional assays with organoids generated with the patient's own tumor cells. In addition to the molecular data from the sequencing offered by other companies, the oncologist will also have previous information regarding the tumor response of that patient to the drugs tested. In this way, there is an increase in the chances of the treatment chosen by the oncologist be effective for the patient. The improvement in patients' quality of life as they undergo chemotherapy sections has an intangible value. In addition, increased treatment efficiency and shorter hospital stay results in considerable savings for health systems overall. As a consequence, larger investments can be made in other sectors, bringing a benefit not only to cancer patients but also to the general population. (AU)