Rosa Rubicondior: Malevolent Design - How Breast Cancer is 'Designed' to Survive

Cell culture plates in the Roeder lab where scientists recently studied gene expression in breast cancer.

Credit: Lori Chertoff.

The Rockefeller University » This molecular switch helps cancer cells survive harsh conditions

Researchers at The Rockefeller University's Laboratory of Biochemistry and Molecular Biology have uncovered the mechanism that enables breast cancer cells not only to withstand environmental stress, but to turn it to their advantage. They have just published their findings in Nature Chemical Biology.

For ID creationists, these findings pose yet another challenge—one typically ignored or waved away as the consequence of ‘sin’, neatly exposing the Discovery Institute’s attempt to persuade US legislators and educators that ID is a genuine scientific alternative. No real science explains inconvenient evidence by invoking fundamentalist doctrine or unevidenced forces inherited from ancient superstition.

The Rockefeller University team has shown that breast cancer cells can override a regulatory factor that normally controls gene expression. The transcription of DNA into mature messenger RNA involves the enzyme RNA polymerase II (POL II), whose activity depends on around 30 subunits. One of these, MED1, normally carries acetyl groups. Without those acetyl groups, MED1 loses its ability to regulate POL II, allowing the enzyme to transcribe genes that help cancer cells survive. Environmental stress deacetylates MED1. In essence, conditions such as low oxygen or elevated temperature—deadly to normal cells—can instead make cancer cells more resilient.

This presents several problems for ID creationists. First, the complexity of a process that could have been far simpler if it had been intentionally designed—yet is repeatedly cited by Discovery Institute fellow Michael J. Behe as evidence for design, despite the obvious fact that good design minimises unnecessary complexity. Second, the process relies on what Discovery Institute fellow William A. Dembski claims as a hallmark of intelligent design: complex, specified genetic information. Without it, cancer cells would likely fail to survive—or at least would be far easier to target with drugs or the body’s own defences.

So here we have, in the Discovery Institute’s own language, both irreducible complexity and complex, specified genetic information—the supposed signatures of an intelligent designer—present in breast cancer cells.

Yet when confronted with such examples, the inference of a benevolent, omniscient designer—generally equated with the god of the Bible or Qur’an—evaporates. At best, the evidence would suggest a malevolent alternative designer over whom the supposed omnipotent, omnibenevolent deity has no control, a being able to interfere at will while the deity is either powerless or indifferent to the suffering that results. And so ID creationism retreats into the realm of primitive fundamentalist superstition, the fearful, demon-haunted imaginings of our species’ infancy.

How big a problem is breast cancer? Breast cancer remains one of the most significant public-health challenges worldwide.

It is the most commonly diagnosed cancer globally (excluding non-melanoma skin cancers).
Around 2.3 million new cases are diagnosed each year worldwide, according to WHO and IARC estimates.
It accounts for roughly one in four cancers in women and is also increasing—though still rare—in men.
Breast cancer is responsible for approximately 670,000 deaths globally each year.
Incidence is highest in high-income countries, but mortality is disproportionately high in low- and middle-income regions, where early detection and treatment access are limited.

Breast cancer is therefore both common and deadly, but the picture has been changing markedly in recent decades.

Progress in diagnosis, treatment, and survival

Medical science has made substantial progress, particularly in the following areas:

Earlier detection

Population screening, especially mammography, has enabled detection of tumours at earlier, more treatable stages.
Improvements in imaging—MRI, digital mammography, ultrasound—have reduced false positives and improved sensitivity.
Public awareness campaigns have led to earlier presentation, improving outcomes.

Better classification of breast cancers

Breast cancer is not a single disease. Advances in genomics and molecular biology have allowed clinicians to distinguish:

Hormone receptor-positive cancers
HER2-positive cancers
Triple-negative cancers
Additional subtypes within these broad groups

This classification has enabled precision treatment, matching therapies to the tumour’s molecular profile.

Major improvements in treatment

Treatment has diversified and become more targeted:

Hormone therapies, such as tamoxifen and aromatase inhibitors
HER2-targeted therapies, e.g., trastuzumab, pertuzumab, and later antibody–drug conjugates
CDK4/6 inhibitors
PARP inhibitors for BRCA-related cancers
More precise radiotherapy
Less invasive surgery, thanks to earlier detection and better imaging
Advances in reconstructive techniques improving post-surgical quality of life

These innovations have significantly increased survival.

Falling mortality rates in many countries

Since the late 1980s and early 1990s:

Mortality from breast cancer has fallen by 30–40% in many high-income nations.
The UK, US, Canada, Australia, and much of Western Europe have all seen sustained declines.
Survival rates vary by stage, but five-year survival now exceeds 85% in many countries, and can exceed 90% where screening and treatment access are optimal.

Persistent inequalities

Not all regions have benefited equally:

Many low-income countries have rising incidence and stagnant or rising mortality, largely due to limited screening infrastructure, late diagnosis, and restricted access to modern therapies.
Within high-income countries, socioeconomic and ethnic disparities remain significant.

Overall assessment

Breast cancer remains a major global health issue, particularly for women, but scientific progress has been dramatic:

More cancers are detected early.
Modern therapies are increasingly targeted and effective.
Mortality has dropped sharply where early detection and advanced treatment are widely available.

However, the disease is still responsible for hundreds of thousands of deaths each year, and global inequalities in survival remain substantial.

The Rockefeller University team’s work is explained further in a science news release.

This molecular switch helps cancer cells survive harsh conditions
Cells are regularly faced with environmental stresses that may damage or destroy them. To survive, they quickly adjust their gene expression to protect themselves. This is especially true for cancer cells, which must contend with a microenvironment that is inherently uncongenial. Yet they can thrive in these conditions, turning on genes that help them to develop into larger tumors or spread to other parts of the body.
How cancer cells manage to turn a dire situation into an advantage has been unknown. Rockefeller researchers thought clues might lie in teasing out how the gene transcription machinery senses the stressful environment and then changes course. Now they’ve discovered a molecular switch in breast cancer cells that reprograms the genetic production line towards tumor growth and stress resistance.

This finding, published in Nature Chemical Biology, presents a potential new target for cancer therapies.
This previously unknown transcription-level mechanism helps the cancer cells survive stressful conditions, so targeting it could disrupt a key survival mechanism that some cancers rely on. It’s another example of how basic research can open promising therapeutic avenues.

,Ran Lin, first author
Laboratory of Biochemistry and Molecular Biology
Rockefeller University
New York, NY, USA

We found that this molecular switch is mediated by a generic transcription complex normally required for all protein-coding genes. But what was most unexpected is that its individual subunits can be repurposed for several physiological functions—including a function that allows cancer cells to survive and grow in high-stress environments.

Robert Roeder, co-corresponding author
Laboratory of Biochemistry and Molecular Biology
The Rockefeller University
New York, NY, USA.

Transcription services

RNA polymerase II, aka Pol II, is the machinery that transcribes protein-coding genes in eukaryotes. Discovered by Roeder decades ago, Pol II often teams up with the Mediator complex—a large transcriptional coactivator protein composed of 30 subunits—to initiate transcription, the first step in creating mature RNA. Further edits can come from so-called post-transcriptional modifications, which can also alter gene expression.

One key subunit of the complex is MED1, which is essential for Pol II transcription in different types of cells—including estrogen receptor–positive breast cancer (ER+ BC), one of the most common forms of the disease.

Previous research on ER+ BC from Roeder’s lab has shown that estrogen receptor interactions with MED1 drive gene activation—so much so that they can render otherwise promising cancer drugs ineffective. These findings made Lin wonder whether MED1 played a role in helping cancer cells stay alive, and even thrive, in stressful conditions.

Lin decided to explore whether MED1 is acetylated. Acetylation is a biochemical modification that involves adding an acetyl group to a protein, which can alter its function, and is increasingly being recognized for its seemingly influential role in tumor development, metastasis, and drug resistance.

After determining that MED1 is indeed acetylated, he next aimed to understand how this modification influences its function, especially under cellular stress. They subjected the cells to different types of stress conditions, including hypoxia (lack of oxygen), oxidative stress, and thermal stress.

Altering the acetyls

They discovered that under stress, a protein called SIRT1 removes acetyl groups from normal MED1. This “deacetylation” enables MED1 to interact more efficiently with Pol II, leading to the elevated potential for activation of protective genes.

They also created a mutant form of MED1 that lacked six specific acetylation sites, making it unable to be acetylated. They then introduced this mutant protein into ER+ breast cancer cells in which the endogenous MED1 had been removed using CRISPR.

They found that regardless of how the MED1 became deacetylated—either through stressful conditions or by removing its ability to become acetylated—the breast cancer cells with deacetylated MED1 formed faster-growing and more stress-resistant tumors.

Our work reveals that the acetylation and deacetylation of MED1 act as a regulatory switch that helps cancer cells reprogram transcription in response to stress, supporting both survival and growth. In cancer—particularly in ER+ breast cancer—this pathway may be co-opted or intensified to support abnormal growth and survival. We hope these insights will inform future drug development, especially for breast cancers and possibly other malignancies that rely on stress-induced gene reprogramming.

,Ran Lin.

This MED1 regulatory pathway appears to be part of a wider paradigm in which acetylation regulates transcription factors. Our earlier work on p53 helped establish that principle. Continuing to probe these basic mechanisms is what allows us to identify pathways that may eventually be leveraged for therapeutic purposes.

Robert Roeder.

Publication:
Lin, R., Mo, Y., Barrows, D. et al.
MED1 IDR deacetylation controls stress responsive genes through RNA Pol II recruitment. Nat Chem Biol (2025). https://doi.org/10.1038/s41589-025-02035-7

Abstract
Cells fine-tune gene expression in response to cellular stress, a process critical for tumorigenesis. However, mechanisms governing stress-responsive transcription remain incompletely understood. This study shows that the MED1 subunit of the Mediator coactivator complex is acetylated in its intrinsically disordered region (IDR). Under stress, SIRT1 associates with the super elongation complex to deacetylate MED1 in promoter-proximal regions. The deacetylated (or acetylation-defective mutant) MED1 amplified stress-activated cytoprotective genes and rescued stress-suppressed growth-supportive genes in estrogen-receptor-positive breast cancer (ER+ BC) cells. Mechanistically, deacetylated MED1 promotes chromatin incorporation of RNA polymerase II (Pol II) through IDR-mediated interactions. Functionally, ER+ BC cells with deacetylated MED1 exhibit faster growth and enhanced stress resistance in culture and in an orthotopic mouse model. These findings advance our understanding of Pol II regulation under cellular stress and potentially suggest therapeutic strategies targeting oncogenic transcription driven by MED1 and Mediator.

Lin, R., Mo, Y., Barrows, D. et al.
MED1 IDR deacetylation controls stress responsive genes through RNA Pol II recruitment. Nat Chem Biol (2025). https://doi.org/10.1038/s41589-025-02035-7

© 2025 Springer Nature Ltd.
Reprinted under the terms of s60 of the Copyright, Designs and Patents Act 1988.

Findings like these continue to demonstrate the power of genuine biological science to illuminate the inner workings of life, even when those workings reveal processes that are anything but benevolent. Cancer, far from being a sign of design, is a stark reminder of the evolutionary compromises and vulnerabilities baked into our biology. The ability of breast cancer cells to co-opt stress responses and harness them for survival is precisely what we would expect from an unguided, opportunistic process shaped by selection acting at the cellular level—not from a perfect designer with benevolent intentions.

Medical science has nevertheless made enormous strides in reducing the toll of breast cancer. Earlier detection, better imaging, precision therapies and a far more detailed understanding of cancer biology have all contributed to falling mortality in much of the developed world. But the burden remains heavy, especially where access to modern healthcare is limited, and cancers that exploit sophisticated stress-response pathways—like those uncovered in this study—continue to pose serious challenges.

What we see, once again, is that progress comes not from invoking supernatural agencies but from patient, painstaking research grounded in evidence. The more we uncover about how cancer cells survive and adapt, the better equipped we become to defeat them. And the more these discoveries accumulate, the clearer it becomes that Intelligent Design offers neither explanation nor utility—only an attempt to repackage ancient superstition as science, while real scientists carry on with the work that actually saves lives.

Meanwhile ID Creationism staggers on trying to find ways to ignore, dismiss or explain away observable evidence instead, of like a real science, explaining it and any claim it had to be regarded as a real science continues to look more and more like the intended deception it always was.

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