ABSTRACT
Despite relevant medical advancements, metastatic breast cancer remains an uncurable disease. HER2 signaling conditions tumor behavior and treatment strategies of HER2 expressing breast cancer. Cancer treatment guidelines uniformly identify dual blockade with pertuzumab and trastuzumab plus a taxane as best first line and trastuzumab emtansine as preferred second line choice. However, there is no prospectively designed available study focusing on the sequence and outcomes of patients treated with T-DM1 following the triplet. In the following report, data concerning a wide series of patients treated in a real-life setting are presented. Results obtained in terms of response and median progression free survival suggests a significant role for T-DM1 in disease control of metastatic HER2 expressing breast cancer.
ABSTRACT
Palbociclib is a potent cyclin-dependent kinase (CDK)4/6 inhibitor that disrupts cell cycle progression and has been recently approved in combination with an aromatase inhibitor or fulvestrant as first- and second-line treatment in hormone receptor (HR)+, human epidermal growth factor receptor (HER)2- metastatic breast cancer. There is evidence that palbociclib may reverse endocrine therapy resistance and that it may also be added to ongoing endocrine therapy beyond progression to obtain clinical benefit. The aim of the present study was to explore this possibility in 5 patients who received palbociclib + fulvestrant following disease progression while under treatment with fulvestrant alone. The median progression-free survival was not reached during a median follow-up of 25 months, and the most frequent best response was stable disease. Three patients remained under treatment on the last re-evaluation. All patients had highly endocrine-sensitive disease and had previously received fulvestrant for ≥12 months. The hypothesis that a selected subpopulation of patients with HR+/HER2- metastatic breast cancer may benefit from the addition of palbociclib to ongoing endocrine therapy beyond disease progression merits further investigation.
ABSTRACT
The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored cell membrane receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. Its expression is increased in many human cancers, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), and correlates with a poor prognosis and early invasion and metastasis. uPAR is able to control, through a cross-talk with tyrosine kinase receptors, the shift between tumor dormancy and proliferation, that usually precedes metastasis formation. Therefore, we investigated the role of uPAR expression in RAS mutated NSCLC and CRC cells. In this study we provided evidence, for the first time, that RAS mutational condition is functionally correlated to uPAR overexpression in NSCLC and CRC cancer cell lines and patient-derived tissue samples. Moreover, oncogenic features related to uPAR overexpression in RAS mutated NSCLC and CRC, such as adhesion, migration and metastatic process may be targeted, in vitro and in vivo, by new anti-uPAR small molecules, specific inhibitors of uPAR-vitronectin interaction. Therefore, anti-uPAR drugs could represent an effective pharmacological strategy for NSCLC and CRC patients carrying RAS mutations.
