Table 2 Clinical trials designed in breast tumors for the treatment with SRC kinase inhibitors

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]