Therapeutic Monitoring of Orally Administered, Small-Molecule Anticancer Medications with Tumor-Specific Cellular Protein Targets in Peripheral Fluid Spaces—A Review

Abstract

Orally administered, small-molecule anticancer drugs with tumor-specific cellular protein targets (OACD) have revolutionized oncological pharmacotherapy. Nevertheless, the differences in exposure to these drugs in the systemic circulation and extravascular fluid compartments have led to several cases of therapeutic failure, in addition to posing unknown risks of toxicity. The therapeutic drug monitoring (TDM) of OACDs in therapeutically relevant peripheral fluid compartments is therefore essential. In this work, the available knowledge regarding exposure to OACD concentrations in these fluid spaces is summarized. A review of the literature was conducted by searching Embase, PubMed, and Web of Science for clinical research articles and case reports published between 10 May 2001 and 31 August 2022. Results show that, to date, penetration into cerebrospinal fluid has been studied especially intensively, in addition to breast milk, leukocytes, peripheral blood mononuclear cells, peritoneal fluid, pleural fluid, saliva and semen. The typical clinical indications of peripheral fluid TDM of OACDs were (1) primary malignancy, (2) secondary malignancy, (3) mental disorder, and (4) the assessment of toxicity. Liquid chromatography–tandem mass spectrometry was most commonly applied for analysis. The TDM of OACDs in therapeutically relevant peripheral fluid spaces is often indispensable for efficient and safe treatments.

A liquid chromatography-miniature mass spectrometry (LC-Mini MS) method for quantitative analysis of risperidone and 9-hydroxyrisperidone in plasma

“…Clinical TDM drugs have rich diversity and typically include immunosuppressants, antipsychotic drugs, anticancer medications, antibiotics, monoclonal antibodies, etc. [1][2][3][4][5] The quantitation of antipsychotic drugs, due to their relatively narrow therapeutic range and the significant individually different therapeutic effects, has attracted more and more attention in the field of TDM. [6][7][8] Risperidone is a secondgeneration atypical antipsychotic drug, which has good therapeutic effects on schizophrenia and other mental diseases.…”

Pioneering the Photoactive Relevance of Quinazolinone–Fullereropyrrolidine Nanohybrids To Address Chemotherapeutic Resistance in Cancer

“…FDA-approved pyrimidine anticancer drugs such as gefitinib and erlotinib are developed based on these mechanisms. Additionally, compounds such as ceritinib, ruxolitinib, and others show promise as potent anticancer agents by targeting various enzymes and signaling pathways involved in cancer growth and differentiation. , By synthetically harnessing other bioactive synthons with these active pharmacophores, molecular hybrids capable of stronger biological potency can be achieved. Since photodynamic therapy (PDT) has revolutionized noninvasive target cancer therapy, our approach has been to cultivate new hybrid molecular systems by covalently functionalizing quinazolinones with competent bioactive chromophores such as fullerenes.…”