Combined PARP and SHP2 Inhibition Slows Breast Cancer

MD Anderson researchers report a preclinical approach that overcomes treatment resistance in multiple breast cancer models.

Updated on Nov. 12, 2026 in Cancer

Isometric editorial illustration of glass culture flasks and petri dishes on a laboratory bench, representing a preclinical breast cancer research combination approach. — MD Anderson researchers reported that combining PARP and SHP2 inhibition slowed breast cancer growth more than either drug alone in preclinical models, published in Cancer Research. AI Illustration. Upload story photo >

Researchers at The University of Texas MD Anderson Cancer Center developed a combination approach that targets the PARP and SHP2 proteins at the same time, which significantly slowed cancer growth in multiple preclinical breast cancer models compared with either drug alone. The findings, published in Cancer Research, were co-led by Anil Korkut, Ph.D.

Why it matters

Many cancers eventually resist therapy because tumor cells activate compensatory survival pathways, a process known as adaptive response. The study suggests that blocking two of these pathways together may help address resistance, though the results remain preclinical and require further validation.

The study is preclinical, with the strongest effects seen in cells that had developed resistance to therapy and carried DNA repair defects. Whether the combination performs similarly in human patients remains unknown and will require further validation.

The players

The University of Texas MD Anderson Cancer Center

A major cancer research and treatment institution in Houston that is consistently ranked among the top cancer centers in the United States.

Anil Korkut, Ph.D.

A researcher at MD Anderson who co-led the study introducing the TargetScore algorithm and the combination approach.

The details

TargetScore, a computational biology algorithm developed at UT MD Anderson, analyzed breast cancer cells exposed to treatment targeting MCL1. The algorithm predicted that the PARP and SHP2 pathways help cancer cells resist apoptosis, and the researchers then targeted both proteins together or individually to test those predictions.

Article reporting the study findings was published on OncLive on November 12, 2026.

Big Picture

The work builds on the clinical use of PARP inhibitors in DNA repair-deficient breast cancers, where resistance often limits long-term benefit. Pairing PARP inhibition with SHP2 blockade offers a preclinical route to extend that benefit in patients whose tumors have already developed resistance.

For patients with breast cancer, this research does not change current treatment options, since the findings are preclinical. Any future combination therapy would first need clinical trials to confirm its safety and whether it extends benefit beyond existing drugs.

The takeaway

Resistance to targeted therapy often comes from cancer cells switching on backup survival pathways. Targeting more than one pathway at once is a strategy researchers are now testing, though it remains years from clinical use.