# Use of Small-Molecule Inhibitors of CILK1 and AURKA as Cilia-Promoting Drugs to Decelerate Medulloblastoma Cell Replication

## TL;DR

This paper explores drugs that promote cilia formation to slow down the replication of medulloblastoma cancer cells.

## Contribution

The study introduces a novel method using AI to identify cilia-promoting drugs and validates their anti-cancer effects.

## Key findings

- Alvocidib and Alisertib increase cilia frequency in cancer cells.
- These drugs significantly reduce medulloblastoma cell replication.
- Gemini AI outperformed other models in literature search accuracy.

## Abstract

Background/Objective: The primary cilium is the sensory organelle of a cell and a dynamic membrane protrusion during the cell cycle. It originates from the centriole at G0/G1 and undergoes disassembly to release centrioles for spindle formation before a cell enters mitosis, thereby serving as a cell cycle checkpoint. Cancer cells that undergo rapid cell cycle and replication have a low ciliation rate. In this study, we aimed to identify cilia-promoting drugs that can accelerate ciliation and decelerate replication of cancer cells. Methods: To perform a comprehensive and efficient literature search on drugs that can promote ciliation, we developed an intelligent process that integrates either the GPT 4 Turbo, Gemini 1.5 Pro, or Claude 3.5 Haiku application programming interfaces (APIs) into a PubMed scraper that we coded, enabling the large language models (LLMs) to directly query articles for predefined user questions. We evaluated the performance of this intelligent literature search based on metrics and tested the effect of two candidate drugs on ciliation and proliferation of medulloblastoma cells. Results: Gemini was the best model overall, as it balanced high accuracy with solid precision and recall scores. Among the top candidate drugs identified are Alvocidib and Alisertib, small-molecule inhibitors of CILK1 and AURKA, respectively. Here, we show that both kinase inhibitors can effectively increase cilia frequency and significantly decrease the replication of medulloblastoma cells. Conclusions: The results demonstrated the potential of using cilia-promoting drugs, such as Alvocidib and Alisertib, to suppress cancer cell replication. Additionally, it shows the massive benefits of integrating accessible large language models to conduct sweeping, rapid, and accurate literature searches.