Paola Del Mar Torres-Cruz

Therapeutic strategies in pancreatic cancer are largely limited to chemotherapy alone. While targeted therapeutics are in development, their activity when used in combination remain uncertain at this time. The most common pro-oncogene in PDAC is KRAS with alterations in exon 2 (G12D) representing 40% of the population.  Additionally, Methylthioadenosine Phosphorylase (MTAP) has been shown to recycle nucleotides, whereas the loss of MTAP seen in 30% of PDAC has been shown to support metabolic cycling to promote cancer progression. Using patient-derived organoid models, we will assay the synergy indexes of dual targeting of KRAS (G12D) and MTAP using a first in class targeted inhibitors MRTX1133 and MRTX1719, respectively.