Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2024 Jun 21;10:68. doi: 10.1038/s41540-024-00394-w

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2024, corrected publication 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Fig. 4 — A Heatmap for DDRi:non-DDRi combination synergies. Mean of synergy and mean of killrate were calculated for each MoA group for all cell lines in the certain indication group. Combinations that had synergy >0,5 were highlighted with turquoise color. The size of the circles represents the combination’s effect on cell viability. Bracketed numbers after the name of the indication at the left represent the number of cell lines in that group. The plot shows that CHKi combined with ERKi were strongly synergistic in brain tumor cell lines. PRKDCi represented a strong synergistic effect with EM/TM inhibitors. PRKDCi:NFKBi combinations were highly synergistic and at least cytostatic in many of the indications except for kidney, skin, and colon cancer cell lines. NFKBi performed well in combination with the WEE1 inhibitor only in kidney and melanoma cell lines. Protein synthesis inhibiting drugs (PIK3/AKT/MTORi) combined with WEE1i seems to be strongly synergistic in brain cancer cell lines only. B Indication-specific synergistic patterns of DDRi:DDRi combinations. Charts are representing some examples of non-synergistic (ATMi:PARPi, ATMi:PRKDCi, WEE1i:PARPi), moderately synergistic (WEE1i:PRKDCi), and strongly synergistic combinations (ATMi:CHKi, ATMi:ATRi). The latter combinations had a strong cell viability decreasing effect too in all indications, which suggests that ATM inhibitors in combination with ATR and CHK targeting compounds have a cytotoxic effect. Mean of synergy and killrate values were calculated for each MoA group for all cell lines categorized into indication groups. C Intra-DDR module combination synergy map reveals frequent intra-DDR module synergy except for PARPi and PRKDCi (except PRKDCi:WEE1i) combinations. Turquoise lines: strongly synergistic relationships between compounds where the cell-killing effect of the combination supported the synergistic phenomenon. Black continuous lines: moderately synergistic combinations, where an intermediate cell viability decrease was observed. Dashed lines: weak or non-synergistic combinations. CSNK Casein kinase, DDR DNA damage repair, EM/TM epigenetic/transcriptomic modulation, ERK extracellular signal-regulated kinase, JAK/STAT Janus kinase/signal transducers and activators of transcription, NFKB NF-kappa B, PIK3/AKT/MTOR phosphatidylinositol 3’ -kinase(PI3K)-AKT-mTOR, TK/RTK tyrosine kinase/receptor tyrosine kinase.