3 The “magic bullet” concept, described by Paul Ehrlich, originally referred to a chemical that specifically targeted microorganisms. The clinical application of ADCs utilizes mAbs, which were first described in 1975. This category of drug is one of the fastest growing classes of cancer therapeutics in the past few decades. This novel approach combines the specificity of a monoclonal antibody (mAb) with the high potency of small molecules and has the potential to improve cancer treatment. 2 However, not all patients may benefit from immune checkpoint blockade, as only about 40% of triple-negative tumors are PD-L1 positive, and the tumor will ultimately become resistant to first-line therapy, necessitating the development of additional beneficial targeted therapies.Īntibody–drug conjugates (ADC) are immunoconjugate agents engineered to deliver potent small molecules preferentially to cancer cells. As a first-line treatment for patients with PD-L1-positive metastatic TNBC, the PD-L1 inhibitor, atezolizumab plus nab-paclitaxel, showed a survival benefit compared with nab-paclitaxel alone. Although recent efforts to characterize TNBC tumors based on the profiling of its transcriptome, proteome, genome, epigenome, and immunological microenvironment are helping to increase understanding of the molecular heterogeneity of TNBC, 1 the development of novel treatment strategies is an area of unmet clinical need. Aside from germline BRCA1/2 deficiency, which now has an approved targeted therapy, PARP inhibition, and programmed cell death ligand 1 (PD-L1)-positive tumors, for which immunotherapy with a PD-L1 inhibitor is now approved, attempts to identify biomarkers that can help guide treatment decisions with targeted therapies have yet to improve the outcomes of patients with metastatic TNBC, and cytotoxic chemotherapy remains the mainstay of treatment. 1 TNBC is often the most challenging subtype of breast cancer to treat for various clinical and biological reasons. Clinically, TNBC is often an aggressive tumor subtype associated with an earlier age of onset, higher rate of relapse, and a relatively short survival of 10–13 months from the time of metastasis. Triple negative breast cancer (TNBC) is a heterogeneous tumor subtype conventionally defined by the absence of expression of the estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 ( HER2) amplification, and accounts for approximately 15–20% of all breast carcinomas.
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