Table 2.

Clinical trials designed in breast tumors for the treatment with SRC kinase inhibitors

Drug name	Targets	Combination	Phase	Study purpose	Patient selection	Efficacy	Study outcome	Main reference
Bosutinib	All SFKs and ABL	/	II	To evaluate the toxicity and efficiency of Bosutinib	Locally advanced or metastatic BC pretreated with chemotherapy	PR = 5.5%, SD = 32.9%	Bosutinib showed promising efficacy and was generally well tolerated	[114]
		Exemestane	II	To evaluate the efficiency of Bosutinib plus exemestane as second-line therapy	Locally advanced or metastatic HR-positive/HER2-negative BC	PR = 2%, SD = 7%	An unfavorable risk–benefit profile was observed	115
		Letrozole	II	To evaluate the efficiency of Bosutinib plus letrozole as second-line therapy	Locally advanced or metastatic HR-positive/HER2-negative BC	PR = 6% SD = 6%	An unfavorable risk–benefit ratio was obtained	[116]
		Capecitabine	I	To evaluate the maximum tolerated dose, safety, and efficacy of Bosutinib plus capecitabine	Advanced/metastatic BC	/	Limited efficacy was observed	[117]
Dasatinib	SRC, LCK, FYN, and YES	/	II	To evaluate the efficacy and safety of Dasatinib monotherapy	Advanced HER2 + /ER + BC	PR = 4% SD = 13%	Limited single-agent activity was observed	[120]
		/	II	To assess the efficacy and safety of single-agent Dasatinib	Advanced TNBC	PR = 4.7% SD = 27.9%	Single-agent Dasatinib has limited activity in unselected patients with TNBC	[39]
		/	II	To evaluate efficiency and tolerability of Dasatinib combining with real-time pharmacodynamic tissue biomarkers	Metastatic BC	/	Single-agent Dasatinib did not exhibit significant antitumor activity in patients with metastatic BC	[121]
		/	II	To assess the efficacy of Dasatinib	Patients with bone-predominant BC metastasis	PR = 4%	Dasatinib was ineffective in controlling bone-predominant metastatic BC in a patient population unselected by molecular markers	[122]
		/	II	To assess the efficiency of Dasatinib combing with gene signature	Metastatic BC with predictive gene signatures	/	None of the predictive gene signatures could define tumor clinical sensitivity to Dasatinib as a single agent	[123]
		Paclitaxel	I	To determine the maximum tolerated dose of paclitaxel and Dasatinib	Metastatic BC	PR = 31% SD = 29%	120 mg daily (Dasatinib) and weekly paclitaxel were recommended	[124]
		Paclitaxel	II	To assess the efficiency of paclitaxel and Dasatinib	HER2-negative metastatic BC	PR = 20%	Study was stopped early due to slow accrual, and this combination showed some clinical activity	[125]
		Capecitabine	I	To assess the toxicity and maximum tolerated dose for Dasatinib plus capecitabine	Advanced BC	PR = 24% SD = 32%	The result supported further study with this combination in patients with advanced BC	[126]
		Letrozole	II	To assess the efficiency of aromatase inhibitor and Dasatinib	HR-positive metastatic BC	CBR = 71%	Letrozole plus Dasatinib was well tolerated	[127]
		Zolendronic acid	I/II	To determine the clinical efficacy of Dasatinib combined with zoledronic acid	Bone-predominant HER2-negative metastatic BC	CR + PR = 23% SD = 13%	Combination therapy was well tolerated and produced responses in bone in patients with HR-positive tumors	[129]
		Trastuzumab and paclitaxel	I	To assess the efficiency of trastuzumab plus paclitaxel in combination with Dasatinib	HER2-positive metastatic BC	/	This combination was feasible, and showed synergistic effect in patient with trastuzumab resistance	[130]
		Trastuzumab and paclitaxel	II	To assess the synergistic effect of Dasatinib and trastuzumab and paclitaxel	HER2-positive metastatic BC	PR = 69% SD = 10%	The combination was active with an objective response rate of almost 80%	[131]
Saracatinib	SRC and ABL	/	II	To evaluate the efficacy and safety of Saracatinib monotherapy	Unselected metastatic HR-negative BC	No response	Saracatinib did not show significant single-agent activity in HR-negative metastatic BC patients	[134]

CR complete response, PR partial response, SD stable disease, CBR CR + PR + SD