Medicine› Oncology› Pancreatic and Hepatic Oncology Research

Pancreatic cancer — KRAS G12D

Submitted 2026-10-18

Field: Medicine › OncologyIllustrative exampleArea: pancreatic cancerTarget: KRAS G12DStage: preclinical✦ AI inferred reasoning

Hypothesis

Combining a KRAS inhibitor with a SHP2 inhibitor would delay resistance in G12D-mutant PDAC organoids.

What failed

No delay in resistance vs. monotherapy across 3 organoid lines at 12 weeks.

Why

Bypass signaling through RTK upregulation, independent of the SHP2 pathway — the combination targeted the wrong resistance mechanism.

Research ideas from this failure

Unvetted lead — read the papers

New hypotheses this failure suggests, each with a crucial experiment, a rival explanation of the original result, and the papers it rests on. Written by AI from paper titles and abstracts found on OpenAlex (and Europe PMC, for life and health sciences).

Not available for example entries: this one describes an invented experiment, and ideas built on it would be fiction.

Related failures (1)

Matched on shared genes, mechanisms and ways of failing as well as wording. Each shows why it matched — treat these as leads rather than verdicts.

pancreatic cancerTREM2
Blocking TREM2 would repolarise tumour-associated macrophages and restore T-cell infiltration in PDAC allografts.
Macrophage phenotype shifted on flow cytometry but tumour growth curves showed no separation from isotype control.
Why it matched: same research area · failed the same way: Bypassed by compensatory signalling

Links in published research

Where this experiment's genes are known to matter outside its own research area, and the papers behind those links. Sources: Open Targets Platform and Europe PMC.