From Bench to Bedside: Lessons Learned in Translating Preclinical Studies in Cancer Drug Development

 
Blogger's Note: numerous ovarian cancer studies referenced

open access

"The development of targeted agents in oncology has rapidly expanded over the past 2 decades and has led to clinically significant improvements in the treatment of numerous cancers. Unfortunately, not all success at the bench in preclinical experiments has translated to success at the bedside. As preclinical studies shift toward defining proof of mechanism, patient selection, and rational drug combinations, it is critical to understand the lessons learned from prior translational studies to gain an understanding of prior drug development successes and failures. By learning from prior drug development, future translational studies will provide more clinically relevant data, and the underlying hope is that the clinical success rate will improve and the treatment of patients with ineffective targeted therapy will be limited.

Because standard chemotherapy demonstrates limited efficacy against a range of adult solid tumor malignancies, there has been an impetus toward the development of targeted agents in oncology. Likewise, there has been a shift of translational research away from simple screening studies of activity in preclinical models toward studies that define proof of mechanism, patient selection, and rational drug combinations. These strategies are substantially changing the preclinical rationale used to drive clinical development. Although these more robust preclinical studies have successfully guided the development of targeted agents in several tumor types, not all success at the “bench” has translated to success at the “bedside.” As preclinical models become more sophisticated, translational studies of targeted agents will have the potential to produce more clinically relevant data not only to guide “go/no-go” decisions but also to investigate resistance pathways and rational drug combinations. This review will provide examples of lessons learned from prior preclinical studies used in the development of targeted agents and addresses strategies moving forward..... 

Sections:

Epidermal Growth Factor Receptor Targeted Agents

Lessons Learned From EGFR Inhibition

Targeted Therapies Against Drivers of Oncogenesis

Lessons Learned in Targeted Therapies Against Drivers of Oncogenesis

Targeting Angiogenesis

Lessons Learned From Angiogenesis

Targeting Basic Cellular Processes

Lessons Learned From Targeting Basic Cellular Processes

Preclinical Models and Prediction of Pharmacokinetics and Toxicity

Limitations in Preclinical Models and Future Directions