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Radiopharmaceutical therapy in the era of precision medicine
George Sgouros1, David M Goldenberg2
1Division of Nuclear Medicine, Dept. of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Abstract:
Precision medicine is the selection of a treatment modality that is specifically tailored to the genetic and phenotypic characteristics of a particular patient's disease. In cancer, the objective is to treat with agents that inhibit cell signalling pathways that drive uncontrolled proliferation and dissemination of the disease. To overcome the eventual resistance to pathway inhibition therapy, this treatment modality has been combined with chemotherapy. We propose that pathway inhibition therapy is more rationally combined with radiopharmaceutical therapy (RPT), a cytotoxic treatment that is also targeted. RPT exploits pharmaceuticals that either bind specifically to tumours or accumulate by a broad array of physiological mechanisms indigenous to the neoplastic cells to deliver radiation specifically to these cells. Consistent with pathway inhibition therapy and in contrast to chemotherapy, RPT is well tolerated. However, the potential of RPT has not been fully exploited; for the most part, treatment has been implemented without using the ability to customise RPT by imaging and deriving individual patient tumour and normal organ radiation absorbed doses. These are more closely related to biological response and their determination should enable RPT treatment administration to maximum therapeutic benefit by treating to normal organ tolerance or demonstrating futility via tumour dosimetry. This is the essence of precision medicine.
Insights
Precision medicine tailors cancer treatments to individual patients. Combining targeted pathway inhibitors with radiopharmaceutical therapy (RPT) offers a more effective and tolerable approach than chemotherapy.
Area of Science:
- Oncology
- Radiopharmaceutical Therapy
- Precision Medicine
Background:
- Precision medicine revolutionizes cancer care by tailoring treatments to individual genetic and phenotypic profiles.
- Current strategies combine pathway inhibition therapy with chemotherapy to combat cancer proliferation and resistance.
- Pathway inhibition therapy aims to block cancer-driving signaling pathways, but resistance remains a challenge.
Purpose of the Study:
- To propose radiopharmaceutical therapy (RPT) as a more rational combination partner for pathway inhibition therapy in cancer treatment.
- To highlight the potential of RPT in delivering targeted radiation to cancer cells.
- To emphasize the underutilization of personalized dosimetry in optimizing RPT efficacy and safety.
Main Methods:
- Reviewing the principles of precision medicine and targeted cancer therapies.
- Analyzing the mechanisms of action for pathway inhibition therapy, chemotherapy, and RPT.
- Discussing the role of personalized dosimetry (tumor and normal organ radiation absorbed doses) in RPT administration.
- Comparing the tolerability and efficacy of RPT with traditional chemotherapy.
Main Results:
- Radiopharmaceutical therapy (RPT) is a targeted cytotoxic treatment that can be customized for individual patients.
- RPT is well-tolerated, similar to pathway inhibition therapy, and contrasts favorably with chemotherapy.
- Personalized dosimetry derived from imaging can optimize RPT to maximize therapeutic benefit while minimizing toxicity.
- Implementing customized RPT can lead to treatment guided by normal organ tolerance or futility demonstrated by tumor dosimetry.
Conclusions:
- Combining pathway inhibition therapy with RPT represents a more precise and effective strategy in precision oncology.
- Personalized dosimetry is crucial for unlocking the full potential of RPT in cancer treatment.
- This approach allows for treatment optimization based on individual biological responses, aligning with the core principles of precision medicine.
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