Testing Adaptive Therapy Protocols Using Gemcitabine and Capecitabine in a Preclinical Model of Endocrine-Resistant...

Area of Science:

• Oncology
• Cancer Therapeutics
• Mathematical Biology

Background:

• Adaptive therapy is an ecologically inspired cancer treatment approach.
• It aims to overcome drug resistance and reduce toxicity by managing tumor heterogeneity.
• This strategy prioritizes patient survival and quality of life over maximum tumor cell kill.

Purpose of the Study:

• To evaluate adaptive therapy using capecitabine and gemcitabine in an endocrine-resistant breast cancer model.
• To compare adaptive therapy regimens against maximum tolerated dose (MTD) and high-dose combination therapy.
• To prepare for a future clinical trial investigating adaptive therapy.

Main Methods:

• A mouse xenograft model using endocrine-resistant MCF7 breast cancer cells was employed.
• Adaptive therapy was tested using capecitabine, gemcitabine, or their combination.
• Regimens included dose modulation and intermittent adaptive therapies, with drug alternation investigated.

Main Results:

• Dose modulation with capecitabine alone showed a non-significant increase in survival time compared to MTD.
• Alternating capecitabine and gemcitabine in both dose modulation and intermittent adaptive therapies significantly increased survival time versus high-dose combination therapy.
• Reduced dosing in adaptive therapy led to decreased tumor proliferation and increased apoptosis compared to high-dose therapy.

Conclusions:

• Adaptive therapy, particularly two-drug alternating regimens, shows significant promise in improving survival time and tumor response.
• This approach favors slower-growing tumors and offers a viable alternative to continuous high-dose chemotherapy.
• Adaptive therapy warrants further investigation in clinical settings for cancer treatment.