Dr. Yadav on the Synergy of a Novel Combination in Uterine Serous Carcinoma

Ghanshyam Yadav, MD
Published: Friday, Apr 12, 2019



Ghanshyam Yadav, MD, first-year resident, Baylor College of Medicine, discusses the synergy of a novel combination in the treatment of patients with HER2-overexpressing uterine serous carcinoma.

Across tumor types, there has been significant interest in targeting cell surface receptors, which led researchers to explore the combination of the PARP inhibitor olaparib (Lynparza) and the TKI neratinib (Nerlynx) in this patient population. Recent data in the breast cancer realm suggested that inhibiting PI3K, a downstream molecule in that pathway, also had activity in BRCA. Researchers were hopeful that a similar, synergistic effect would occur with the combination of olaparib and neratinib in HER2-overexpressing uterine serous carcinoma.

Initially, treatment with a PARP inhibitor led to increased HER2 expression on the cell surface, so study investigators were hopeful that adding a HER2-targeted agent would be useful, Yadav says. Subsequently, investigators realized neratinib also increased PAR, the active part of PARP, proving that the agents act synergistically. Notably, Yadav adds, this benefit appears to be limited to cases of HER2 overexpression—the combination was tried in cell lines with low HER2 expression, and they did not find the same results.
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Ghanshyam Yadav, MD, first-year resident, Baylor College of Medicine, discusses the synergy of a novel combination in the treatment of patients with HER2-overexpressing uterine serous carcinoma.

Across tumor types, there has been significant interest in targeting cell surface receptors, which led researchers to explore the combination of the PARP inhibitor olaparib (Lynparza) and the TKI neratinib (Nerlynx) in this patient population. Recent data in the breast cancer realm suggested that inhibiting PI3K, a downstream molecule in that pathway, also had activity in BRCA. Researchers were hopeful that a similar, synergistic effect would occur with the combination of olaparib and neratinib in HER2-overexpressing uterine serous carcinoma.

Initially, treatment with a PARP inhibitor led to increased HER2 expression on the cell surface, so study investigators were hopeful that adding a HER2-targeted agent would be useful, Yadav says. Subsequently, investigators realized neratinib also increased PAR, the active part of PARP, proving that the agents act synergistically. Notably, Yadav adds, this benefit appears to be limited to cases of HER2 overexpression—the combination was tried in cell lines with low HER2 expression, and they did not find the same results.



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