Stromal Senescence following Treatment with the CDK4/6 Inhibitor Palbociclib Alters the Lung Metastatic Niche and Increases Metastasis of Drug-Resistant Mammary Cancer Cells.

Background: CDK4/6 inhibitors (CDKi) have improved disease control in hormone-receptor-positive, HER2-negative metastatic breast cancer, but most patients develop progressive disease.

Methods: We asked whether host stromal senescence after CDK4/6 inhibition affects metastatic seeding and growth of CDKi-resistant mammary cancer cells by using the p16-INK-ATTAC mouse model of inducible senolysis.

Results: Palbociclib pretreatment of naïve mice increased lung seeding of CDKi-resistant syngeneic mammary cancer cells, and this effect was reversed by depletion of host senescent cells.

An evaluation of palbociclib as a breast cancer treatment option: a current update.

Introduction: Patients with hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer have benefitted from treatment with palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor capable of selectively targeting mechanisms of cell cycle progression that contribute to tumor cell proliferation. Palbociclib use in this setting demonstrates improved progression-free survival when given in combination with aromatase inhibitors or fulvestrant.

Areas Covered: The authors describe the current state of research surrounding palbociclib use in breast cancer, present evidence supporting a role for palbociclib in additional subtypes of metastatic breast cancer such as HER2-positive (HER2+) and triple-negative, report ongoing clinical trials aimed at expanding the scope of use for palbociclib, and discuss expected clinical results that will better inform decisions on including palbociclib as a part of breast cancer treatment strategies.

Short- and Long-Term Effects of CDK4/6 Inhibition on Early-Stage Breast Cancer.

CDK4/6 inhibitors are used in the treatment of advanced estrogen receptor (ER)(+) breast cancer. Their efficacy in ER(-) and early-stage breast cancer is currently under investigation. Here, we show that palbociclib, a CDK4/6 inhibitor, can inhibit both progression of ductal carcinoma (DCIS) and growth of invasive disease in both an ER(-) basal breast cancer model (MCFDCIS) and an ER(+) luminal model (MCF7 intraductal injection).

A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid cancer.

Germline mutations in the tumor suppressor gene, BRCA-1 associated protein (BAP1), underlie a tumor predisposition syndrome characterized by increased risk for numerous cancers including uveal melanoma, melanocytic tumors and mesothelioma, among others. In the present study we report the identification of a novel germline BAP1 mutation, c.1777C>T, which produces a truncated BAP1 protein product and segregates with cancer.