How Is Personalized Cancer Therapy Evolving?

Personalized medicine focuses on tailoring medication to a patient’s genetic and biochemical makeup, enabling more effective treatment with fewer side effects.

In oncology, this can include leveraging information about a patient’s specific cancer-linked genetic mutations to design or select the therapy or drug combination that is most likely to be effective.

Technology Networks spoke to Dr. Funda Meric-Bernstam, chair of the Department of Investigational Cancer Therapeutics and medical director of the Institute for Personalized Cancer Therapy at the University of Texas MD Anderson Cancer Center, about the landscape of personalized cancer therapy.

Meric-Bernstam also explored the biomarker-based approaches that are guiding personalized treatment strategies and shared insights into the areas that she believes will have the biggest impact on the field over the next few years.

Katie Brighton (KB): Can you give us a brief overview of what the landscape of personalized cancer therapy looks like currently?

Dr. Funda Meric-Bernstam (FMB): In the past decade, there have been many advances in personalized cancer therapy. We went from sequencing a handful of genes to routinely being able to offer next-generation sequencing in larger panels of several hundreds of genes, with whole exome and whole genome sequencing also being explored. We went from recognizing that there are genomic alterations that are drivers of cancer to having multiple drugs approved for diseases with specific genomic alterations.

We have also seen wide adoption of “basket trials” that give greater access to novel genomically formed therapies, as well as selected drugs approved in a “tumor agnostic” fashion—meaning patients with any tumor type could potentially benefit from the therapy if they have a specific genomic alteration.

However, personalized cancer therapy is still in its infancy and is likely to be a lot more impactful over the next few years with new targets, new drugs, novel combinations, comprehensive molecular profiling, and better systems to understand and interpret these results emerging.

KB: Can you discuss how your research into molecular therapeutics informs clinical trial design and the development of personalized treatment strategies?

FMB: Over the years, we have recognized that few patients have durable responses with single-agent therapy even in the context of a genomic driver. Therefore, we have focused on not only identifying novel drivers but also identifying biomarkers of response and resistance, as well as the mechanisms behind resistance to emerging therapies. Understanding the mechanisms of resistance may help design rational combinations to achieve durable responses.

KB: You’ve helped MD Anderson to establish a framework for assessing genomic actionability, a Precision Oncology Decision Support Team, and databases to facilitate genotype-selected trials—can you explain these systems and how they benefit the patient in a little more detail?

FMB: We are fortunate that we are in an information explosion with new drugs, new biomarkers, and many innovative clinical trials.

We have worked to make this information more accessible to oncologists to ensure we provide a framework for understanding what alternate molecular alterations are actionable, what the potential therapeutic options are, and what clinical trials are available.

Some of these efforts are local solutions, such as building an innovative clinical trial portfolio, clinical trial alerts, molecular tumor boards, and other decision support efforts.

Some of these are broader, such as building a framework for interpreting the results more broadly, or helping to build national clinical trials such as ComboMATCH.

KB: What emerging biomarker strategies do you believe are most promising for guiding treatment in difficult-to-treat cancers?

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FMB: In precision oncology, we have focused initially on genomically informed therapy. Ultimately, the impact of genomic testing depends on the availability of effective drugs.

We expect that a large number of patients who previously did not have “actionable genomic alterations” will benefit from precision oncology once KRAS becomes widely more actionable, and similarly, we will see the impact of other next-generation inhibitors and other new agents as technology and drug development evolves.

For example, several new drug classes targeting the cell surface—such as antibody–drug conjugates, bispecific antibodies, and CAR T cells—are in development and have dramatically transformed outcomes in some diseases already.

Precision oncology using novel assays such as RNA panels, whole transcriptome analysis, proteomics, or multiplex immunohistochemistry, plus looking at ways to personalize immunotherapy, could bring the next wave of accomplishments.

KB: What do you see as the major challenges in the clinical implementation of precision oncology?

FMB: As biomarkers and the therapeutic landscape evolves, one of the key issues remains decision support.  It is important that health care providers know what assays to order, how to interpret them, and that patients are aware of therapeutic options locally and beyond.

KB: In your opinion, what advances in technology, data science, or collaboration will have the greatest impact on personalized cancer therapy over the next few years?

FMB: Over the next few years there will be advances in many areas. First, undoubtedly there will be an explosion of novel therapies with opportunities to personalize them better. Secondly, molecular testing will evolve with more comprehensive testing. Third, I hope we'll be able to integrate information better, and with interinstitutional and academic-industry collaborations learn more from each patient, and leverage newer tools such as AI-based tools for discovery as well as decision support.