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The Study

Abstract A047: KRAS G12C and G12D mutants exhibit distinct conformational flexibility in the helix 3–switch 2 pocket that drives differential protein function

In simple terms

This study is like taking apart two different toy cars to see how their insides work differently. It shows one car’s engine part moves in a weird way compared to the other, but it doesn’t tell you which car will break down faster on the road.

0%

Analysis score

0/ 0

Maximum 0 for a computational/algorithm study.

Where the score came from

Reporting0
Methodology19
Publication100
Statistical31
Study type (basis of the score)
Computational/Algorithm Study
Level 5 - Expert opinion
What’s the bottom line?

Two common cancer mutations in the KRAS protein, G12D and G12C, look different at the molecular level, making G12D better at turning on cancer signals.

Where does this study sit?

Reviews of RCTs (Meta-analyses)

Max 100

Randomized Trials

Max 90

Reviews of Cohort Studies

Max 85

Cohort Studies

Max 72

Reviews of Case-Control Studies

Max 63

Case-Control Studies

Max 58

Cross-Sectional & Case Series

Max 50

Expert Opinion

Max 5
StrongerWeaker
Expert Opinion
Level 5
0

0 / 100

Quality score

Based on clinical experience or non-systematic literature reviews. The lowest level of evidence as they are most susceptible to bias and personal perspective.

Cannot establish causation

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Key takeaways

Summary

Based on the study abstract and findings.

  1. 1Yes — stronger binding means G12D may drive cancer more aggressively and respond differently to drugs than G12C.
  2. 2KRASG12D binds the cancer signal protein PI3Kα 2x stronger than KRASG12C, and 3x stronger than normal KRAS.
  3. 3A drug called BBO-11534 works better on G12D than G12C.

Score breakdown, methodology, conflicts of interest, evidence analysis & raw study data

Publication

Journal

Cancer Research

Year

2026

Authors

Alok K. Sharma, Megan Rigby, Marco Tonelli, Nicole Fer, Patrick A Alexander, Jun Pei, Yue Yang, Dana Rabara, Erik K. Larsen, Brian P Smith, R. Ma, V. Kumari, M. Dyba, F. Lightstone, Bin Wang, P. Beltran, Eli Wallace, Andrew G Stephen, D. Nissley, F. McCormick, A. Maciag

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