Early cancer research focused primarily on chemical carcinogenesis in rat models and helped establish clear causal links between environmental chemicals and increased risk of cancer in exposed populations. And although cancer research has gotten significantly more sophisticated over the past century, researchers are signaling that chemical carcinogenesis models of cancer are resurging in relevance once again.

Thanks to recent breakthroughs in DNA sequencing, scholars now have the proper tools to “dissect complete tumor genome architectures” and it is better understood that “chemically induced cancers in the mouse carry a high point mutation load and mutation signatures that reflect the causative agent used for tumor induction,” according to McCreery et al in their article, “Chemical Carcinogenesis Models of Cancer: Back to the Future” published in the Annual Review of Cancer Biology. 

Therefore, chemical carcinogen models have the potential to significantly improve the study of environmental impacts on the development of cancers – including matching profiles of mutations in human cancers to their source. Furthermore, the understanding of mutation signatures also may help researchers better understand the possible linkage between certain cancer treatments, particularly radiation and chemotherapy, and the presence of tumor relapses or the development of secondary malignancies.

Beyond the benefits associated with identifying the causes behind mutagen signatures, carcinogen models may also help answer some longstanding questions in the field of cancer biology. McCreery et al suggest that chemical carcinogenesis models have the potential to:

• Define how different cell tissues and cell types interact with environmental agents linked to human cancers.
• Determine how different cells within the same tissue can give rise to tumors of different histological subtypes, or lesions or the same subtype that have different propensities for malignant progression.
• Provide valuable analysis related to tumor heterogeneity at the genetic level as exemplified by the emergence of subclones carrying particular mutations.
• Further develop and identify successful combinations of targeted, chemo-, and immunotherapy drugs in a preclinical setting.

In vivo chemical carcinogenesis models may just have what it takes for researchers to better understand the necessary pathways to prevent, treat and ultimately cure human cancer.