Organoids

A promising tool to elucidate the molecular characteristics of HCC are patient-derived organoids (PDOs), three-dimensional cultures of cells that self-organise according to tissue-specific patterns and can be used to test the susceptibility of a specific tumour to anticancer agents. In this study, PDOs for HCC will be developed that closely resemble the tumour microenvironment in vivo and mimic the crosstalk of the gut-liver axis to establish a correlation with patient prognosis and test the efficacy of available systemic therapies.

COSENSE-1 is an unblinded, phase II, single-armed, single center feasibility study for using a functional precision medicine platform to select oxaliplatin-based versus irinotecan-based chemotherapy regimens, for male and female participants aged 18 and older, with microsatellite stable (MSS)/proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC), that is incurable or not resectable with curative intent.

Demonstrate the existence of neurodevelopmental alterations in organoids derived from samples of patients with bipolar disorder (BD) with a neurodevelopmental (ND) component, compared with patients with bipolar disorder (BD) without an ND component.

Malignant hydrothorax and ascitic fluid in advanced breast cancer often arise from metastasis to the lungs, pleura, or liver. Patients with this condition experience rapid disease progression and multidrug resistance, facing limited treatment options. Clinical guidelines offer various therapies based on molecular subtypes; however, their effectiveness can be hindered by prior treatments, patient health, and tumor evolution. Current evaluations of treatment efficacy typically take two cycles, delaying the recognition of ineffective therapies and resulting in unnecessary side effects and costs. Organoid models present a promising solution, accurately replicating tumor structure and cellular diversity compared to traditional methods. These patient-derived models facilitate improved drug sensitivity testing, leading to more personalized treatment plans. In this study, 90 patients diagnosed with metastatic breast cancer accompanied by hydrothorax and ascitic fluid will be recruited. Patient-derived organoids will be used to assess the sensitivity of chemotherapy regimens, including Doxorubicin, Carboplatin, Cyclophosphamide, and Paclitaxel, along with targeted therapies such as Herceptin and Pertuzumab.

Breast cancer is the most common malignancy in women worldwide. Patients with breast cancer are often diagnosed at later stages and have a strong desire for breast conservation, necessitating neoadjuvant chemotherapy. Tumors of different molecular subtypes and individual variations among patients lead to significant differences in treatment efficacy. Precise assessment of patients' responses to treatment regimens is imperative in advancing prognosis of breast cancer. In this study, 58 patients diagnosed with breast cancer and scheduled for neoadjuvant therapy will be recruited. Patient-derived organoids from their tumor biopsies will be utilized to evaluate the sensitivity of chemotherapy regimen. These drugs primarily include Doxorubicin, Carboplatin, Cyclophosphamide, Paclitaxel, as well as targeted therapies such as Herceptin and Pertuzumab.

The human body inhabits a complex consortium of different microbes which together form the microbiota. Virtually every surface of the human body is colonized by a distinct microbiota, forming complex communities. An increasing number of research results indicates that changes in the microbiota can have vast effects on the health of its host. Most studies investigating the microbiota were conducted on animals, as many interventions and investigations cannot be performed on humans due to ethical considerations. This raises the question if findings from experimental studies are translational and can benefit patients. That becomes especially apparent when trying to dissect molecular mechanisms involved in this fine-tuned interplay between nutrients, the microbiota, and its host. By establishing human organoid cultures from the large and small intestine that can be exposed to microbes and/or microbial products with subsequent transcriptomic, epigenetic and immunological analysis, the investigators aim to generate findings with high translational potential with new insights into the complex interaction of the microbiota, the host and its immune system.

Development of tools to predict patients chemo-sensitivity and identification of corresponding biomarkers is an urgent challenge for BC patients lacking targeted therapies, such as TNBC, or for patients experiencing relapse after adjuvant chemotherapy or targeted therapies. The refinement of 3D-cultivation techniques, experienced in the last decade, has allowed cultivation of patients-derived cancer cells in organotypic structures, named patient-derived organoids (PDO), which preserve histologic, genomic and transcriptomic features of primary tumors. PDO allow propagation, pharmacological treatment and genetic manipulation of patients-derived cancer cells in a close to physiology setting, thus representing a promising tool in the development of personalized therapies

The clinical incidence of intrahepatic cholangiocarcinoma (ICC) is high and insidious, and the prognosis of advanced patients is poor. The clinical manifestations of traditional chemotherapy GC and emerging targeted therapy are different in most patients, and there is still no effective scheme to evaluate the differences in individual patient reactivity. Patient-derived tumor organoids (PDO) are 3D-cultured tissues based on tumor cell dryness that reproduce a variety of biological characteristics of parental tumors in vitro and have similar drug responsiveness to tumors in vivo. This project plans to use clinical cases and optimized organoid culture system to first construct relevant organoids from unresectable ICC patient puncture samples. Secondly, based on the organoid model of intrahepatic cholangiocarcinoma, the clinical efficacy of GC regimen was predicted, and in vitro and in vivo drug screening was conducted to explore the guidance of patient-derived tumor organoids for clinical treatment. Then, multi-omics data of organoids and in vitro and in vivo drug efficacy evaluation model were used to explore the drug resistance genes of intrahepatic cholangiocarcinoma, providing the basis for personalized drug screening and efficacy evaluation of intrahepatic cholangiocarcinoma.