ICE Bioscience Posters

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The development of PARP inhibitors (PARPi) has revolutionized cancer treatment, particularly for BRCA1/2 deficient tumors. However, the emergence of PARPi resistance poses a significant challenge. Our study aimed to explore the mechanisms of this resistance, focusing on the role of DNA end resection.

We induced resistance in the MDA-MB-468 cell line using Talazoparib and Olaparib, creating in vivo models to evaluate drug sensitivity. RNA-seq analysis identified significant gene expression changes in resistant cells, hinting at altered signaling pathways.

Our results showed increased resistance indices and poor drug response in resistant cell lines, confirming resistance development. Establishing over 40 drug-resistant cell lines, our platform is poised to facilitate the advancement of PARP targeted therapies, offering insights into overcoming PARPi resistance in cancer treatment.

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The CB1 receptor, a key component of the endocannabinoid system (ECS), is crucial in appetite control, pain perception, mood regulation, obesity, and diabetes. In oncology, the ECS plays a pivotal role in tumors' growth, development, and metastasis, with the activation or inhibition of the CB1 potentially exerting substantial impacts on cancer treatment and prevention. In vitro and in vivo modes are established to understand the signaling pathways of CB1, interactions with other cellular components and the development of more selective novel drugs with fewer side effects. CB1 receptor activation inhibits Forskolin-stimulated adenylate cyclase by G protein (Gαi/o) and increases the phosphorylation of extracellular signal-regulated kinase 1/2 (pERK1/2) via G protein-dependent and β-arrestin-dependent pathways. Here we constructed an integrated experimental cascade, including in vitro HTRF cAMP assay and β-arretin2 NanoBiT assay, to conduct the high throughput hit-to-lead compound screening, agonist, antagonist and inverse agonist validation. Meanwhile, several CDX modes are constructed for promisingly conducting in-vivo experiments and biomarker detection. Thus, ICE supports multiple approaches for helping the drug discovery and development of CB1 to facilitate the treatment of multiple diseases.

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In the specific fields of genetics, epigenetics is the study of heritable changes in gene expression and cell phenotype caused by DNA methylation, histone modification and regulation of non-coding RNA without altering the DNA sequence. Abnormal methylation modification of mRNA and abnormal expression of miRNA and other non-coding RNA often promote the tumorigenesis. Therefore, tumor epigenetic therapy has become an urgent research direction for scholars.

ICE Bioscience has established an epigenetic screening platform for exploration on tumor epigenetic therapy. The platform mainly includes methylation screening platform, acetylation screening platform and mRNA screening platform. It includes about 100 types of epigenetic hot targets, which allows the platform being supportive for preclinical research and anticancer drug validation. Meanwhile, several biochemical and cell-based assays are demonstrated for promisingly conducting in-vitro experiments. Thus, ICE Bioscience epigenetic platform can support tumorigenesis research and new-generation anti-tumor drug development.

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Antibody-drug conjugates (ADCs) are an innovative promising class of cancer therapeutics. ADCs are comprised three key components of an antibody (monoclonal antibody or bispecific antibody), a cytotoxic payload or other novel types of payload, and a linker. ADCs integrate chemotherapy and immunotherapy by combining the potency of payloads with the specificity of antibodies.

ICE Bioscience has established a biological and DMPK integrated platform for ADC screening and evaluation. The platform is dedicated to support a comprehensive service portfolio with various aspects of ADC development projects.