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. 2023 Jun 13;5(3):zcad029. doi: 10.1093/narcan/zcad029

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© The Author(s) 2023. Published by Oxford University Press on behalf of NAR Cancer.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 5. — WEE1 and PKMYT1 co-inhibition kills patient-derived ovarian cancer organoids. (A) Characteristics of the selected set of long-term organoid cultures. NACT, neoadjuvant platinum-based chemotherapy. Mutations: fs, frameshift; stop, stop-gain; miss, missense mutation; splicing, splicing isoform mutation; LOH, loss of heterozygosity. Copy number columns indicate number of gene copies per cell; the numbers in red highlight the amplification of the gene. (B) Representative micrographs of HGSC organoids from patient EOC884. The organoids were treated with increasing doses of RP-6306 and adavosertib for 7 days. White masks label CellTox Green-negative live organoids and green masks label CellTox Green-positive dead organoids. Scale bar indicates 1 mm. (C) Quantification of the viability of EOC884 organoids after 7 days of the drug combination treatment illustrated in panel (B). Values in heat map cells present the percentage of live organoids relative to DMSO-treated control. Mean, n = 3.(D)ZIP synergy plots for adavosertib and RP-6306 interaction in the dose matrix viability testing in EOC884 organoids in panel (C). Interaction was classified as synergistic if ZIP score ≥10. (E) Quantification of the viability in panel of HGSC organoids after 7 days of the drug combination treatment illustrated in panel (B). Values in heat map cells present the percentage of live organoids relative to DMSO-treated control. Mean, n = 3. (F) ZIP synergy plots for adavosertib and RP-6306 interaction in the dose matrix viability testing in panel of HGSC (E). Interaction was classified as synergistic if ZIP score ≥10.