No abstract

The diagnosis of brain metastasis (BrM) has historically been a dooming diagnosis that is nothing less than a death sentence, with few treatment options for palliation or prolonging life. Among the few treatment options available, brain radiotherapy (RT) and surgical resection have been the backbone of therapy. Within the past couple of years, immunotherapy (IT), alone and in combination with traditional treatments, has emerged as a reckoning force to combat the spread of BrM and shrink tumor burden. This review compiles recent reports describing the potential role of IT in the treatment of BrM in various cancers. It also examines the impact of the tumor microenvironment of BrM on regulating the spread of cancer and the role IT can play in mitigating that spread. Lastly, this review also focuses on the future of IT and new clinical trials pushing the boundaries of IT in BrM.

To conduct a systematic review of the comparative efficacy of various psychotropic medications for the treatment of disruptive behavior (DBs) in youths. To this aim, we systematically reviewed randomized clinical trials (RCTs) of various psychotropic medications targeting symptoms of DBs and applied network meta-analysis to investigate their relative efficacy. Fifty-five RCTs meeting the inclusion criteria were selected. To predict and interpret relative treatment efficacy, we compared the efficacy of various psychotropic medications prescribed for DB symptoms based on their mechanism of action. Network meta-analysis revealed that for reducing DBs, second-generation antipsychotics, stimulants, and non-stimulant ADHD medications were more efficacious than placebo, and second-generation antipsychotics were the most efficacious. The dopaminergic modulation of top-down inhibitory process by these medications is discussed in this review. This study offers information on the relative efficacy of various psychotropic medications for the treatment of DB, and insight into a potential neurobiological underpinning for those symptoms. It also illustrates the potential utility of these neurobiological mechanisms as a target for future treatment studies.

Lung cancer is the leading cause of cancer-related deaths worldwide. Small cell lung cancer (SCLC) is an aggressive subtype of lung cancer. The overall survival rate of SCLC is dismal owing to early metastasis, chemoresistance, higher rate of recurrence, and lack of available treatment options. Although some immunotherapeutic drugs have been approved for SCLC, they are effective only in a small fraction of the patient population. This necessitates the quest to find promising vulnerabilities against SCLC. Bioinformatic analysis on SCLC data set in the backdrop of various immune checkpoint regulators revealed B7-H3 as a promising target. The bioinformatics data was recapitulated in SCLC cell lines and human SCLC tissues. To delineate the effects of B7-H3 targeting, we performed CRISPR-Cas9 mediated B7-H3 knockout in SCLC cell lines. B7-H3 knockout in SCLC cells showed a decrease in colony formation, migration, and wound healing properties. Our results suggest that deletion of B7-H3 decrease the functional activities and activation of oncogenic signaling pathways, such as Erk, Akt, and Stat3. Further, we assessed if B7-H3 regulates SCLC metabolism. Preliminary data showed that B7-H3 knockout in SCLC cells inhibits glucose uptake, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR), suggesting its role in SCLC metabolic reprogramming. Altogether, our data indicate that B7-H3 plays a crucial role in SCLC pathogenesis and could serve as a potential therapeutic target for SCLC. Citation Format: Mahek Fatima, Parvez Khan, Asad Ur Rehman, Md Arafat Khan, Shailendra Kumar Maurya, Aatiya Ahmad, Mohd Ali Zaidi, Shailendra Gautam, Subodh Lele, Surinder Kumar Batra, Mohd Wasim Nasser. B7-H3 mediated metabolic reprogramming promotes small cell lung cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 289.