Opinion: Tackling drug resistance must become biotech’s next frontier

When we treat cancer patients, their disease can overcome treatment through its innate capacity to adapt. This is at the heart of drug resistance, attributable for 90% of the 600,000 cancer-related deaths per year in the U.S. alone.

As a neurosurgeon and immunotherapy researcher, I have seen remarkable progress in how we treat cancer and many other complex diseases. Targeted therapies, precision diagnostics and immunotherapies have reshaped outcomes for patients who, until recently, would have had very limited options. These advancements have fundamentally changed what modern medicine can achieve.

Yet with all of the progress we’ve achieved, one issue has remained strikingly consistent: Therapies that work impressively at first often lose their effectiveness over time. Tumors or pathogens adapt, pathways shift and diseases circumvent even our most sophisticated treatments. In some cases these disorders simply worsen, while in others they become resistant to treatment. When faced with diminishing efficacy, clinicians and patients are forced to pivot, often with fewer options and a narrower therapeutic window.

Drug resistance is not confined to any single area of medicine. It is a universal challenge that affects oncology, infectious diseases, autoimmune disorders and many chronic conditions, limiting the durability of therapies and slowing progress across our industry. If we want to sustain and build on the gains we have made, we must treat drug resistance as a central scientific priority rather than an unavoidable complication.

At Kairos Pharma, the company I founded in 2013 to focus on this issue, our mission is to understand why resistance emerges and to develop strategies that restore sensitivity to existing therapies. Although our work is centered on oncology, the broader implications of addressing resistance extend well beyond cancer. In many ways, resistance biology represents one of the most important frontiers in modern drug development.

Drug resistance arises from a predictable and deeply rooted biological principle: survival adaptation. When a therapy disrupts a disease process, cells modify their behavior to restore equilibrium. In cancer, this may occur through new mutations, alternative signaling routes, interactions with stromal or immune cells or microenvironmental changes that protect the tumor from treatment pressure.

Bacterial resistance to antibiotics follows similar adaptive logic. Immune pathways evolve under pressure from biologic therapies. Even chronic metabolic diseases demonstrate compensatory mechanisms that erode long-term treatment effects.

While it is not unique to oncology, drug resistance in cancer can be particularly fierce, and the clinical consequences are substantial. Patients experience relapse or diminished response. Treatment windows narrow. Therapeutic regimens must be changed or intensified. And from a development standpoint, resistance contributes significantly to rising research and development costs with extended timelines, because drug developers must continually create new agents to recapture ground that was previously gained.

Although resistance often appears inevitable, it does not have to be. Historically, our field has not approached resistance as a direct therapeutic target. That is beginning to change, and I believe this shift will redefine how we think about drug durability.

Much of our research centers on the idea that resistance is not simply an endpoint but a biological process that can be interrupted. One example is our candidate ENV-105, which is designed to block a resistance-associated pathway we see emerge in multiple cancers. Its purpose is not to replace existing therapies but to help restore their effectiveness, which is the broader direction I believe drug development needs to move toward across the industry.

This perspective changes the development paradigm. Rather than discarding therapies once resistance appears, we can intervene to extend their utility. This approach has the potential to improve patient outcomes by maintaining control longer, reducing the need for rapid therapy cycling and enhancing the effectiveness of combination strategies.

It also encourages a more integrated and collaborative research environment. Resistance biology is multifaceted and requires contributions from academic laboratories, biotechnology innovators and large pharmaceutical companies. When these groups work together early in the development process, it becomes possible to design therapies that anticipate resistance mechanisms.

As cancer is treated, it becomes more resistant as it becomes more stem cell–like. One can view it as the stem-like cells surviving the treatment, while the more differentiated cells are killed off. Cancer stem cells are equipped to resist toxins like their normal stem cell counterpart. In the case of cancer stem cells, these ‘toxins’ include radiation and therapeutic drugs.

This beneficial ability of stem cells to resist natural toxins enables their “evil twin,” cancer stem cells, to resist therapy. ENV-105 works to differentiate these stem-like cancer cells to make them vulnerable to cancer drugs. In essence, resistance therapy is a cancer stem cell differentiating therapy.

Cancer often highlights the challenge of drug resistance most visibly, but the same patterns emerge across medicine. Antibiotic resistance continues to threaten global health. Autoimmune therapies lose durability as immune systems recalibrate. Chronic diseases reveal compensatory pathways that diminish long-term treatment effects.

Addressing resistance across these areas could transform patient care. It would help therapies maintain their benefit longer, reduce the clinical and economic burden associated with therapy changes and allow drug developers to build on existing advances rather than constantly reinventing classes of medicines.

Ultimately, overcoming drug resistance may be one of the defining scientific opportunities of the next decade. It is essential not only for improving outcomes but for ensuring that the remarkable progress we have made in modern medicine can be sustained.

By elevating drug resistance as a core focus of research and development, we can extend the life of today’s therapies, strengthen future innovations and offer patients a more stable and hopeful path forward.