Related Experiment Video
Updated: Mar 29, 2026
In Vitro Evaluation of Oncogenic Transformation in Human Mammary Epithelial Cells
Published on: September 24, 2020
Dissecting histological transformation
Ethan M Earlie1, Eric E Gardner2, Harold Varmus3
1Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Department of Systems & Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
Abstract:
The adaptive nature of cancer is a major obstacle limiting durable treatment responses. Histological transformation (HT) is a process whereby one cancer changes into a categorically different tumor type, often following treatment with targeted therapy. Best characterized in lung and prostate adenocarcinomas, HT is particularly disconcerting because the resultant cancer no longer depends on the initial oncogenic driver program, is therapeutically recalcitrant, and is often highly metastatic. Partly because HT is technically difficult to study, this process remains poorly described. As newer therapies broaden the scope of oncogenic drivers that can be targeted, HT may become more prevalent, highlighting the need for further research to dissect these phenomena. We propose that modern experimental and analytical tools present an opportunity to advance our understanding and improve our clinical management of histologically transforming cancers.
Insights
Cancer can adapt and change into a new type, called histological transformation (HT), especially after targeted therapy. This adaptive cancer is hard to treat and may spread, requiring new research methods.
Area of Science:
- Oncology
- Cancer Biology
- Translational Medicine
Background:
- Cancer's adaptive nature poses a significant challenge to achieving lasting treatment success.
- Histological transformation (HT) involves a cancer changing into a distinct tumor type, often post-targeted therapy.
- HT cancers are refractory to initial treatments, may exhibit increased metastatic potential, and are poorly understood.
Purpose of the Study:
- To highlight the growing clinical challenge of histological transformation (HT) in cancer.
- To emphasize the need for advanced research tools to study HT.
- To propose leveraging modern experimental and analytical techniques to better understand and manage HT cancers.
Main Methods:
- This study proposes the use of modern experimental and analytical tools.
- Focus on dissecting the phenomena of histological transformation.
- Leveraging advanced techniques to study treatment-resistant cancers.
Main Results:
- Histological transformation (HT) results in cancers that are no longer driven by the initial oncogenic pathway.
- These transformed cancers are therapeutically recalcitrant and often highly metastatic.
- Current understanding of HT is limited due to technical difficulties in studying the process.
Conclusions:
- Histological transformation represents a critical mechanism of therapeutic resistance in cancer.
- Advancements in experimental and analytical tools offer a promising avenue for future research.
- Improved understanding of HT is essential for developing effective clinical management strategies for adaptive cancers.
