What’s Hot in 2025: Oncology

mRNA and organoid technologies are advancing new generations of cancer drugs

Sending a message to cancer

The entire world learned about messenger RNA when the SARS-Cov-2 pandemic struck and triggered the rapid development of two highly successfully COVID vaccines based on mRNA technology. But that's only part of the mRNA story. Science has now turned to leveraging mRNA molecules-which carry genetic information from DNA in the nucleus of a cell to the cytoplasm, where proteins are made-for the development of drugs for numerous other diseases, including cancer. Advances in mRNA technology and personalized medicine are helping fuel an arsenal of drugs for solid tumors, including melanoma, where the very companies that brought us mRNA COVID vaccines in 2020-2021 are now testing their skin cancer candidates in the clinic. Other companies, like Abogen Biosciences in Shanghai, are using mRNA to create synthetic mRNA molecules that are delivered with the help of a lipid nanoparticle system. Meanwhile, American biotech Nutcracker Therapeutics, has a candidate composed of three RNA molecules designed to induce a robust anti-tumor T-cell response. Scientists are also using activating LPNs to deliver mRNA encoding chimeric antigen receptor (CAR)s. By activating T cells and delivering the genetic instructions for CARs in a single step, scientists simplify the CAR-T cell manufacturing process. Look for the first mRNA vaccine for cancer in the 2025 as the first step in what could be the mRNA cancer revolution.

Organoids in the immuno-oncology space

Multiple labs have been looking at ways of marrying their 3D organoids to the PDX models used to preclinically test hundreds of immuno-oncology drugs. One of the major impediments holding this integration back is the fact that tumor-derived organoid technology only applies to epithelial cells, while two other critical components of the tumor microenvironment-stromal cells and immune cells-are under-represented. Fortunately, the field is making headway in solving this problem. Different labs, including ours, have started to close the gap by successfully co-culturing tumor organoids with immune cells. This represents a major step forward for immuno-oncology-and brings us closer to fully utilizing PDX organoids as a precision tool that can predict which populations will benefit from selected drugs. (We still need to solve the stromal cell problem, however,) Stay tuned in 2025 for more developments as the fields of organoid science and PDX models begin to merge and take their place on the preclinical cancer research stage.

-Julia Schueler, Therapeutic Area Lead, Oncology, Charles River