Can molecular profiling enhance radiotherapy? Impact of personalized targeted gold nanoparticles on radiosensitivity and imaging of adenoid cystic carcinoma

Abstract

Personalized molecular profiling has an established role in selection of treatment for metastatic disease; however, its role in improving radiosensitivity and functional imaging has not been evaluated. In the current study, we examined molecular profiling as a tool for designing personalized targeted gold nanoparticles (GNP) to serve as dual-modal tumor radiosensitizers and functional imaging enhancers. To this end, molecular profiling of a patient's salivary gland adenoid cystic carcinoma (ACC) was performed, and anaplastic lymphoma kinase (ALK) mutation was detected. The extracted tumor was subcutaneously injected into mice, which were then treated either with radiation, the specific ALK inhibitor crizotinib, or a combination of therapies. One of these combinations, namely, ALK-targeted GNP (via crizotinib coating), was found to enhance radiation treatment, as demonstrated by a significant decrease in tumor volume over 24 days. In parallel, ALK-targeted GNP substantially augmented tumor visualization via computed tomography. The mechanism of radiosensitivity enhancement was mostly related to a diminished cell repair mechanism in tumors, as demonstrated by proliferating cell nuclear antigen staining. These findings indicate that personalized molecular profiling is an effective technique for enhancing cancer theranostics.

Genome analysis and knowledge-driven variant interpretation with TGex

“…TGex was also useful in the analysis of novel disorders and syndromes, establishing the evidence for the clinical validity of the association between genes and emerging disorders [75, 76], and in discovery of predisposition variants to complex diseases (e.g. Parkinson) [77], as well as hereditary cancer (see Clinical use cases section below) and molecular profiling of tumor biopsies [78].…”

Tumor with slow‑developing and recurring lumps of the external ear with skull base and lung metastasis: A case report

“…It is uncertain whether chemotherapy alters the natural course of metastatic ACC at any site ( 23 , 24 ). With further study on the pathogenesis of ACC, more and more gene mutations have been detected, including epidermal growth factor receptor (EGFR), ALK receptor tyrosine kinase ( 25 ) and notch receptor 1 (NOTCH1) ( 26 ). At present, targeted therapies are being developed that may be useful in the treatment of ACC, including ALK-targeted gold nanoparticles and EGFR-tyrosine kinase inhibitor gefitinib ( 6 , 7 ).…”

“…Local recurrence and distant metastasis result in poor long-term survival, with 80–90% of patients succumbing to the disease within 10–15 years ( 28 ). According to the literature, skull base metastasis is a predictor of lower overall survival and higher rate of local recurrence ( 25 ). Further molecular-level investigations are required in order to improve the current understanding of the unique recurrence and metastasis in ACC.…”

Advances in imaging strategies for in vivo tracking of exosomes

“…CT provides superior visualization of bone structures due to the inherent contrast between electron-dense bones and the more permeable surrounding soft tissues (Meir, Shamalov, et al, 2017;Shwartz et al, 2017). Therefore, CT has been used for cell tracking while combined with nanoparticles as labeling agents (Betzer et al, 2014;Betzer et al, 2015;Betzer, Meir, Motiei, Yadid, & Popovtzer, 2017;Betzer, Shilo, Motiei, & Popovtzer, 2019;Betzer, Shilo, et al, 2017;Hazkani et al, 2017;Meir, Betzer, et al, 2017;Meir, Betzer, Barnoy, Motiei, & Popovtzer, 2018;Popovtzer, 2014;Shilo et al, 2015;Shwartz et al, 2017).…”