Table 1 Basic information on novel agents for CRPC patients from ASCO-GU 2023
Classification | Structure | Mechanism | Side effects | Reference |
|---|---|---|---|---|
RDC | utilizes radionuclides energetically chelated to small molecules or monoclonal antibodies designed to target antigens | target and deliver a precise amount of cytotoxic radiation to prostate cancer cells while sparing the surrounding normal tissues | Neutropenia, thrombocytopenia, abdominal pain, increased ALT levels. diarrhea, thrombocytopenia, neutropenia, nausea, fatigue, xerostomia, AST | [1] |
DART | combine variable domains of two antigen-binding segments linked to two independent poly-peptide linkers. Each variable domain is constructed by associating one light-chain and one heavy-chain covalently linked using disulfide bridges. | Recruit and redirect immune effector cells to kill tumor cells or block various signaling pathways by inhibiting either the ligand or the receptor, redirect effector cells against cancer cell targets in a major histocompatibility complex-independent manner, thereby avoiding immune escape strategies of MHC downregulation by cancer cells. | CRS, organ dysfunction, neurotoxicity | [4] |
CAR-T | Autologous T cells genetically modified to contain a specific CAR and an inducible co-stimulatory domain. | CAR-T cells can recognize tumor antigens in an HLA-independent manner, binding to target proteins on tumor surfaces, promoting T cell proliferation and cytokine secretion, as well as the secretion of anti-apoptotic proteins. | On-target/off-tumor toxicity: binding of CAR-T cells to target antigens expressed on normal cells On-target/on-tumor toxicity: CRS | [6] |
AKTi | pyrimidine compounds and alkyl phospholipids | ATP-Competitive AKTi blocks downstream signaling pathways by trapping Akt in a phosphorylated but nonfunctional state, thus inhibiting tumor cell growth, survival, proliferation, and apoptosis. Allosteric AKTi maintains Akt in a locked conformation, blocking the association of Akt and PIP3 at the membrane level, leading to inhibition of Akt activation. | Side effects such as diarrhea, fatigue, nausea, and rash. | [8] |