The establishment and utilization of preclinical animal models constitute a pivotal aspect across all facets of cancer research, indispensably contributing to the comprehension of disease initiation and progression mechanisms, as well as facilitating the development of innovative anti-cancer therapeutic approaches. These models have emerged as crucial bridges between basic and clinical research, offering multifaceted support to clinical investigations. This study initially focuses on the importance and benefits of establishing preclinical animal models, discussing the different types of preclinical animal models and recent advancements in cancer research. It then delves into cancer treatment, studying the characteristics of different stages of tumor development and the development of anti-cancer drugs. By integrating tumor hallmarks and preclinical research, we elaborate on the path of anti-cancer drug development and provide guidance on personalized cancer therapy strategies, including synthetic lethality approaches and novel drugs widely adopted in the field. Ultimately, we summarize a strategic framework for selecting preclinical safety experiments, tailored to experimental modalities and preclinical animal species, and present an outlook on the prospects and challenges associated with preclinical animal models. These models undoubtedly offer new avenues for cancer research, encompassing drug development and personalized anti-cancer protocols. Nevertheless, the road ahead continues to be lengthy and fraught with obstacles. Hence, we encourage researchers to persist in harnessing advanced technologies to refine preclinical animal models, thereby empowering these emerging paradigms to positively impact cancer patient outcomes.

Abnormal cell proliferation and growth leading to cancer primarily result from cumulative genome mutations. Single gene mutations alone do not fully explain cancer onset and progression; instead, clustered mutations—simultaneous occurrences of multiple mutations—are considered to be pivotal in cancer development and advancement. These mutations can affect different genes and pathways, resulting in cells undergoing malignant transformation with multiple functional abnormalities. Clustered mutations influence cancer growth rates, metastatic potential, and drug treatment sensitivity. This summary highlights the various types and characteristics of clustered mutations to understand their associations with carcinogenesis and discusses their potential clinical significance in cancer. As a unique mutation type, clustered mutations may involve genomic instability, DNA repair mechanism defects, and environmental exposures, potentially correlating with responsiveness to immunotherapy. Understanding the characteristics and underlying processes of clustered mutations enhances our comprehension of carcinogenesis and cancer progression, providing new diagnostic and therapeutic approaches for cancer.

Background: The cell cycle, a critical and intricate biological process, comprises various phases, and its dysregulation plays a pivotal role in tumorigenesis and metastasis. The exploration of cell cycle-based molecular subtypes across pan-cancers, along with the application of synthetic lethality concepts, holds promise for advancing cancer therapies. Methods: A pan-cancer analysis was conducted to assess the cell cycle serves as a reliable signature for classifying molecular subtypes and to understand the potential clinical application of genes as potential drug targets based on synthetic lethality. Results: Molecular subtypes derived from cell cycle features in certain cancers, particularly kidney-related malignancies, exhibited distinct immune characteristics. Synthetic lethal interactions within the cell cycle pathway were common, with significant genetic interactions further identifying potential drug targets through the exploitation of genetic relationships with key driver genes. Additionally, miRNAs and lncRNAs may influence the cell cycle through miRNA:mRNA interactions and ceRNA networks, thereby enriching the genetic interaction landscape. Conclusions: These findings suggest that the cell cycle pathway could serve as a promising molecular subtype signature to enhance cancer prognostication and offer potential targets for anticancer drug development through synthetic lethality.