Related Experiment Video
Updated: May 1, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Targeting oncogenic drivers
1Department of Medicine, Roswell Park Cancer Institute, Buffalo, N.Y., USA.
Abstract:
Cancer is a genetic disease caused by a series of somatic and/or germline mutations. The roles of oncogenes and tumor suppressors in cancer molecular origin have been well established. Targeting oncogene products has become an attractive therapeutic strategy with great clinical success, whereas tumor suppressors are considered 'undruggable' because current technology is not able to restore tumor suppressor function in metastatic disease. Although systematic approaches to discover genetic alterations have become available to individual patients, differentiating driver from passenger mutations and identifying and validating drug targets remain challenging. Protein tyrosine kinases play crucial roles in virtually all cellular processes and possess structural features that render them 'druggable'. Monoclonal antibodies and small-molecule inhibitors represent two major classes of targeted therapeutic agents, each possessing its own strength and weakness. Although initial successes have been achieved, targeted therapy faces many challenges that need to be addressed and hurdles to overcome.
Insights
Cancer, a genetic disease, arises from mutations. While targeting oncogenes shows success, tumor suppressors remain challenging. Protein tyrosine kinases offer druggable targets for cancer therapy, but challenges persist in targeted drug development.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Cancer originates from somatic and/or germline mutations, impacting oncogenes and tumor suppressors.
- Targeting oncogene products is a successful therapeutic strategy, but tumor suppressors are considered 'undruggable'.
- Identifying driver mutations and validating drug targets remain challenging despite advances in genetic alteration discovery.
Purpose of the Study:
- To review the established roles of oncogenes and tumor suppressors in cancer.
- To discuss the challenges and potential of targeting protein tyrosine kinases in cancer therapy.
- To evaluate the strengths and weaknesses of monoclonal antibodies and small-molecule inhibitors in targeted cancer treatment.
Main Methods:
- Review of established knowledge on cancer genetics and targeted therapy.
- Analysis of the 'druggability' of protein tyrosine kinases.
- Comparison of monoclonal antibodies and small-molecule inhibitors as targeted agents.
Main Results:
- Oncogene targeting is clinically successful; tumor suppressors are difficult to target.
- Protein tyrosine kinases are crucial and possess druggable features.
- Targeted therapy, using antibodies or small molecules, has shown initial success but faces significant challenges.
Conclusions:
- Targeting oncogenes is effective, but restoring tumor suppressor function in metastatic disease is a major hurdle.
- Protein tyrosine kinases represent promising targets for cancer therapeutics.
- Further research is needed to overcome challenges and optimize targeted cancer therapies.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:57Targeted Cancer Therapies
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:33Cancer-Critical Genes I: Proto-oncogenes
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:18Cancer