A new article was posted today in the Journal of H
Post# of 148162
Abstract
Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer (BC) with a poor prognosis. Current treatment options are limited to surgery, adjuvant chemotherapy and radiotherapy; however, a proportion of patients have missed the surgical window at the time of diagnosis. TNBC is a highly heterogeneous cancer with specific mutations and aberrant activation of signaling pathways. Hence, targeted therapies, such as those targeting DNA repair pathways, androgen receptor signaling pathways, and kinases, represent promising treatment options against TNBC. In addition, immunotherapy has also been demonstrated to improve overall survival and response in TNBC. In this review, we summarize recent key advances in therapeutic strategies based on molecular subtypes in TNBC.
The role of chemokine receptor type 5 (CCR5) in modulating cell migration and the immune microenvironment is a potentially meaningful target in cancer. In the setting of cancer, increased CCR5 expression indicates a risk of tumor invasion and metastasis, and blocking CCR5 showed an exciting result in reducing tumor metastases by greater than 98% in a murine xenograft model [141]. Leronlimab (PRO140 targeting CCR5) initially received fast track FDA approval to treat human immunodeficiency virus infection. Currently, breakthrough therapy designation for leronlimab has been filed with the FDA to treat mTNBC [142]. An ongoing phase Ib/II clinical trial is being conducted to evaluate leronlimab in combination with carboplatin in CCR5-positive mTNBC, and preliminary analysis shows acceptable tolerability and efficacy [143]. The antibodies ipilimumab (NCT03546686) and tremelimumab (NCT02527434), which target CTLA4, have been assessed in TNBC. Lacnotuzumab (NCT02435680, targeting CSF1/MCSF), tigatuzumab (NCT01307891, targeting human death receptor 5), utomilumab (NCT02554812, targeting CD137), and LAG525 (NCT03499899, targeting lymphocyte activation gene-3) are actively being assessed phase II trials of TNBC.
https://jhoonline.biomedcentral.com/articles/...ugbRqW2I1Q