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The Rapidly Changing Landscape in RCC Therapy: What Future Research May Hold

Bradley Carthon, MD, PhD
Published: Wednesday, Oct 24, 2018

Modern research beyond cytokine therapy has elucidated the various immune cells—including T cells, dendritic cells and natural killer (NK) cells—within renal cell tumors.16 In patients with RCC, there is the potential for a specific antitumor immune response and susceptibility to immune attack.23 The immune system modulates the activating and repressive signals that mediate surveillance of foreign antigens and a T-cell response to tumors.24 Tumor antigen-specific T cells have been isolated in peripheral blood of patients with RCC.25,26

Future Directions

Over the last several years, immunotherapy research has focused on inhibition of common targets within the tumor microenvironment.27 Researchers are also looking at additional activating and inhibiting signals that modulate T-cell responses. Further, investigators are exploring ways that tumor cells develop to avoid being recognized and killed by an immune response. This includes altering antigens, warding off natural killer (NK) cells through factors that suppress immunity, and alerting immune checkpoints that would otherwise recognize the tumor as a foreign body.16,28-30

Addressing these mechanisms may allow immune responses to evolve and expand by continually recognizing and recalling tumor antigens, with the potential to improve over time.31 Building upon these findings, research is now examining additional roles for immunotherapies and potentially using them in earlier lines of therapy.32,33 Combination approaches are also actively being studied in clinical trials, whether it is immunotherapy plus immunotherapy or immunotherapy combined with targeted agents.34

The explosion of data from clinical research in RCC has been exciting, but also poses new questions and prompts different approaches to research. Providing long-term survival benefits for those with advanced RCC continues to be a key objective for research, especially as incidence rates continue to rise.35 RCC research is advancing quickly, which may offer hope to patients.

However, in the face of this rapid evolution, several points should be noted. For example, what will the role of single therapeutic options be compared with combinations? How will emerging options apply in frontline and subsequent settings?

As the treatment landscape changes, so too will the design of clinical trials. Future studies should address novel single-agent and combination therapies, and determine whether reliable biomarkers or other measures exist to predict suitable patients prior to starting treatment.

Updated comparator arms should be considered in subsequent-line studies; moreover, appropriate endpoints should be a priority to guide meaningful studies.

Finally, understanding this emerging landscape is important. Informed and mutual decision-making will help ensure that patients and families have guidance on their various treatment options and the necessary support to navigate this exciting time in RCC research and therapeutic options.

This article was written by Dr. Carthon in collaboration with Bristol-Myers Squibb, which he has provided consulting and advisory services for.

References

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