Our Approach
MEDiC is dedicated to the systematic discovery of biomarkers, synthetic lethality, resistant mutations, and novel drug targets for cancer using its proprietary CRISPR functional genomics platform in 3D tumor models. By combining the power of CRISPR functional genomics with the accuracy and translatability of patient tumor-like cancer models, we aim to identify pathways for cancer drug development (Nature, 2020). Our platform allows the generation and cultivation of millions of CRISPR tumor variants in the presence of human T cells designed to attack these tumor variants. This unique co-culture system, fully integrated with CRISPR, enables us to systematically identify both tumor-intrinsic drug targets and immuno-oncological drug targets. Furthermore, we can identify biomarkers, resistance mutations, and genes associated with synthetic lethality.
Developing a cancer drug is like designing a key without knowing which lock it will open
We often do not know biomarkers of cancer drugs to stratify patients
We systematically install CRISPR variants that mimic cancer mutations to measure associations of drugs with ALL the mutations
It leads to the discovery of key genetic features for cancer drug development such as biomarkers, synthetic lethality & resistant mutations as well as novel drug targets
Drug Response, Drug Resistance and Synthetic Lethality in Oncology
Drug Response
In oncology, drug response indicates the effectiveness of cancer treatments, focusing on outcomes like tumor reduction or improved survival. Molecular biomarkers are crucial for predicting patient responses to therapies, enhancing clinical trials by identifying those most likely to benefit. This stratification accelerates the creation of personalized treatments and reduces side effects. For instance, PD-L1 expression levels serve as a biomarker for the effectiveness of immune checkpoint inhibitors in cancers like melanoma and bladder cancer.
Drug Resistance
Drug resistance in cancer occurs when tumor cells bypass the effects of treatments through mechanisms like genetic mutations or changes in the tumor environment. Understanding these resistance pathways is key to creating new cancer drugs. By identifying how resistance develops, researchers can design therapies that outsmart or target these mechanisms. Biomarker research plays a vital role in finding these pathways and creating effective treatments or combinations to combat resistance. The development of advanced tyrosine kinase inhibitors for EGFR-mutated lung cancer exemplifies the success of targeting drug resistance.
Synthetic Lethal Biomarkers
Synthetic lethality in cancer treatment targets gene pairs or pathways, exploiting the fact that blocking one gene can kill cancer cells with specific mutations. Identifying these interactions allows for the development of targeted therapies that are precise and spare healthy cells. This approach is particularly effective for cancers with certain genetic mutations. A key example is the efficacy of PARP inhibitors in cancers with BRCA1 or BRCA2 mutations is a prime example of exploiting synthetic lethality. These inhibitors target a crucial DNA repair pathway, selectively killing cancer cells deficient in BRCA-mediated repair while sparing normal cells.
MEDiC’s proprietary MCAT Discovery Platform utilizing whole-genome CRISPR functional genomics, NGS, and massive high-throughput 3D cancer spheroids screening, enables the identification of biomarkers, resistance mutations, and genes linked to synthetic lethality.