Managing Drug-Resistant Cancers: Charles Darwin's Theory To The Rescue

Antimicrobial resistance is a major health threat that kills more than a million people each year. But cancer—a non-communicable disease—poses a much bigger challenge to global public health by killing ten times as many. The vast majority of those cancer deaths result from resistance to anti-cancer therapies, a phenomenon that mirrors the fatalities associated with antimicrobial resistance.

A perspective shift in the way that the disease is treated, based on the theory of evolution, could change that.

Each year, over 40 million people die from non-communicable diseases. Cancer is the second leading cause of death from non-communicable diseases after heart disease. Around 20 million people worldwide are diagnosed with cancer annually. Half of them will die from it. The odds are sobering: one in five of us will face a cancer diagnosis during our lifetime, and one in nine men and one in twelve women will die as a result, based on estimates from the Global Cancer Statistics 2020. 

The good news is that survival rates are climbing. Over the past four decades, they've risen by as much as 30 percent for several common cancers thanks to screening, early diagnosis, and advancements in surgical and radiation therapies, according to recent reviews. But with global populations ageing and lifespans increasing, cases are projected to surge by 60 percent over the next 20 years. 

In response, governments and private institutions have poured money into cancer research—over US$7 billion between 2016 and 2020 alone, amounting to 29.2 percent of the total research budget. Yet despite this investment, the disease still carries a reputation as a death sentence. One reason? The treatments themselves.

Conventional cancer therapies rely on the “maximum tolerated dose”—the strongest drug dose a patient can withstand. The goal is straightforward: destroy as many cancer cells as possible. But the result is often something else. These treatments also wipe out healthy cells, leaving patients exhausted and vulnerable. Worse, they can give surviving tumour cells a competitive edge. Like bacteria that become antibiotic-resistant, cancer cells can evolve under pressure, becoming resistant to our most aggressive therapies.

It's a grim cycle: high-dose treatment kills off the easy targets, but leaves behind the tough ones. These resilient cells thrive, multiply and return in a more aggressive, drug-resistant form. Combining different treatments can help, but drug resistance remains unavoidable. Around 90 percent of cancer deaths are linked to this kind of evolutionary drug resistance. Yet the standard treatment paradigm remains largely unchanged. 

This is where Charles Darwin enters the oncology ward.

The evolutionary edge

Darwin's theory of evolution describes how life adapts over time through natural selection, mutation, and genetic drift. These same forces operate at cellular levels in all living things. Cancers are made up of billions of competing cells, constantly mutating and responding to their environment. This evolutionary process creates a genetically diverse tumour in which drug-resistant cells can emerge and survive. 

The ability to slice cancerous tissues into thin layers, separate them into individual cells, and sequence their genome has been vital for this revelation.

Understanding this dynamic has inspired a new treatment approach, one that borrows more from ecology than from traditional medicine. Known as adaptive therapy, the idea is simple yet radical: instead of trying to kill every cancer cell, we learn to live with the disease, managing it like a chronic condition.

The model comes from an unexpected place—agriculture. Since circa 1968, farmers have used a strategy to manage pests that allows some pesticide-sensitive insects to survive. These bugs help suppress the resistant population, slowing the spread of pesticide resistance. Applied to cancer, the same logic suggests we can hold treatment-resistant cells in check by preserving a population of drug-sensitive cells.

In practice, adaptive therapy uses fewer and lower doses of drugs, rather than continuously blasting the body with the maximum tolerable amount in an attempt to kill as many cancer cells as possible. The aim is to maintain a balance by shrinking the tumour enough to relieve symptoms, but not so much that resistant cells dominate the field.

This strategy rests on three key conditions:

1. The tumour must contain both drug-sensitive and drug-resistant cells in advanced cancers that are unresponsive to traditional therapies.
2. The sensitive cells must have an evolutionary advantage over the resistant cells in the absence of treatment.
3. The lower-dose treatment must still reduce the overall tumour burden while keeping the resistant cell population in check.

The approach is gaining traction. Clinical trials are already under way for adaptive therapy in prostate, thyroid, and ovarian cancers, as well as melanoma. Early results are promising. One trial for metastatic castration-resistant prostate cancer at the Moffitt Cancer Center in Florida has shown that adaptive therapy can delay tumour progression by over 50 percent compared to the conventional treatment while using barely half the usual drug dose.

Most early studies focused on single drugs. But in the real world, cancers are usually treated with combinations. This has led researchers to borrow another tool, this time from mathematics, to design adaptive therapies for multidrug combinations: game theory. Originally developed to model decision-making in economics and military strategy, game theory is now helping oncologists design drug regimens that anticipate how tumours will evolve and respond over time.

Still, there are hurdles. One of the biggest is identifying the right patients—those with fewer resistant cells seem to respond best. Another challenge is monitoring tumours in real time and adjusting treatments on the fly. Reliable biomarkers are still lacking, and adaptive therapy demands constant surveillance. These limitations are among the main challenges in implementing evolution-based approaches in practice.

Yet the potential is enormous. By treating cancer as an evolving system rather than a static enemy, adaptive therapy could reshape how we manage the disease. The aim isn't to cure cancer outright, but to transform it into something we can live with, like high blood pressure or diabetes.

Darwin's old theory might just open a new chapter in the fight against one of humanity's most persistent killers.

Dr. Anindita Chakrabarty is Associate Professor, Department of Life Sciences, Shiv Nadar Institution of Eminence, Delhi-NCR.

Originally published under Creative Commons by 360info.

(Except for the headline, this story has not been edited by NDTV staff and is published from a syndicated feed.)