FSIP1 enhances the therapeutic sensitivity to CDK4/6 inhibitors in triple-negative breast cancer patients by activating the Nanog pathway.

CDK4/6 inhibitors are routinely recommended agents for the treatment of advanced HRHER2 breast cancer. However, their therapeutic effectiveness in triple-negative breast cancer (TNBC) remains controversial. Here, we observed that the expression level of fibrous sheath interacting protein 1 (FSIP1) could predict the treatment response of TNBC to CDK4/6 inhibitors.

KK-LC-1 as a therapeutic target to eliminate ALDH stem cells in triple negative breast cancer.

Failure to achieve complete elimination of triple negative breast cancer (TNBC) stem cells after adjuvant therapy is associated with poor outcomes. Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem cells (BCSCs), and its enzymatic activity regulates tumor stemness. Identifying upstream targets to control ALDH cells may facilitate TNBC tumor suppression.

CMTM6 overexpression confers trastuzumab resistance in HER2-positive breast cancer.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is characterized by invasive growth, rapid metastasis and chemoresistance. Trastuzumab is an effective treatment for HER2+ breast cancer; however, trastuzumab resistance leads to cancer relapse and metastasis. CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) has been considered as a new immune checkpoint for tumor-induced immunosuppression.

Targeting SOST using a small-molecule compound retards breast cancer bone metastasis.

Background: Breast cancer metastasis to the bone can be exacerbated by osteoporosis, is associated with poor long-term survival, and has limited therapeutic options. Sclerostin (SOST) is an endogenous inhibitor of bone formation, and an attractive target for treatment of osteoporosis. However, it is unclear whether SOST can be used as a therapeutic target for bone metastases of breast cancer, and whether small molecule compounds that target SOST in breast cancer cells can inhibit breast cancer bone metastasis.

DNA mechanical flexibility controls DNA potential to activate cGAS-mediated immune surveillance.

DNA is well-documented to stimulate immune response. However, the nature of the DNA to activate immune surveillance is less understood. Here, we show that the activation of cyclic GMP-AMP synthase (cGAS) depends on DNA mechanical flexibility, which is controlled by DNA-sequence, -damage and -length.

A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer.

Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla.

FSIP1 regulates autophagy in breast cancer.

Fibrous sheath interacting protein 1 (FSIP1) is a cancer antigen expressed in the majority of breast cancer tissues and is associated with poor prognosis. However, the role of FSIP1 in the progression and drug sensitivity of triple-negative breast cancer (TNBC) has not been explored. Here, we show that FSIP1 deficiency by shRNA-mediated knockdown or CRISPR-Cas9-mediated knockout significantly inhibits the proliferation and invasion of TNBC cells and impairs chemotherapy-induced growth inhibition in vivo.