Drug-Resistant Breast Cancer: Dwelling the Hippo Pathway to Manage the Treatment

Figures & data

Figure 1 Hippo pathway gene regulation in (A) Drosophila melanogaster (B) mammals.

Figure 2 Cellular roles of Hippo pathway.

Figure 3 Hippo pathway genes in breast cancer progression.

Table 1 Commonly Used Chemotherapeutic Drugs for Breast Cancer Treatment

List of Drugs	Mode of Action*
Paclitaxel	A plant alkaloid with anti-microtubule activity.
Lapatinib	Synthetic drug that ceases EGFR phosphorylation.
Doxorubicin, Epirubicin	An anthracycline that blocks topoisomerase enzyme.
Cisplatin	Impede DNA replication.
Tamoxifen	Compete with E2 and block its targeted role.
5-Flouro Uracil	Restricts thymidine formation for DNA synthesis.
Capecitabine	Converts to 5-FU.
Carboplatin	Modifies the DNA molecule by forming reactive platinum complexes that inhibit DNA synthesis.
Cyclophosphamide	Crosslinking of RNA and DNA strands leading to protein synthesis inhibition.
Eribulin	Inhibit microtubules that are in their growth phases.
Gemcitabine	Inhibit DNA synthesis by blocking chain elongation.
Ixabepilone	Suppressor of microtubules.
Methotrexate, Amethoterin	Suppress DHFR enzyme activity that leads to DNA, RNA, and protein formation inhibition.
Protein-bound paclitaxel	Nanoparticle bound paclitaxel with the same activity as paclitaxel.

Note: *Curated from ACCC Oncology Drug Database.

Table 2 Hippo Signaling Components and Their Associated Role in Drug-Resistant Breast Cancer

Hippo Signaling Component	Dysregulation	Drugs	References
YAP	Hyperactivation	Lapatinib, CDK 4/6 inhibitors, Paclitaxel, Doxorubicin	[^Citation43^–^Citation54]
TAZ	Hyperactivation	Paclitaxel, Doxorubicin, Lapatinib, CDK 4/6 inhibitors	[^Citation43^–^Citation45,Citation47,Citation48]
hEx	Downregulation	Paclitaxel, Taxol	[^Citation55]
MST	Downregulation	Cisplatin	[^Citation56]
LATS1	Downregulation	Taxol	[^Citation57,Citation58]
LATS2	Downregulation	Doxorubicin, Tamoxifen	[^Citation59,Citation60]

Figure 4 Hippo signaling in regulating chemo-drugs resistance.

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