The Times Australia
The Times World News

.

A new way to organize cancer mutations could lead to better treatment matches for patients

  • Written by Jacqulyne Robichaux, Assistant Professor of Thoracic & Head and Neck Oncology, The University of Texas MD Anderson Cancer Center
A new way to organize cancer mutations could lead to better treatment matches for patients

There are many types of cancer treatments[1]. But which ones work best varies from patient to patient. Currently, doctors determine which treatment to try for a patient based on where in their DNA, or genetic code, the error that caused the cancer is located.

But a new approach that groups patients by the changes in protein structure and function caused by that error, rather than by the location of the changes in DNA, could lead to both more inclusive clinical trials and better treatment matches for patients.

I am part of a team that researches targeted therapies for cancer[2] and ways to make treatment more patient-specific. A recent study[3] by our research team determined that grouping DNA errors by structure may better personalize cancer therapies.

Targeted therapies hone in on cancer cells

Mutations[4] are errors made during cell replication when the genetic material of that cell, or DNA, makes a new copy of itself. These mutations are usually harmless and caught by the cell’s proofreading machinery.

However, the proofreader occasionally fails. And on rare instances, these mutations occur in parts of the DNA called oncogenes[5]. Under normal conditions, oncogenes are essential to normal growth and development, such as fetal organ development[6] and general tissue repair and maintenance[7]. But when mutations cause oncogenes to signal for unregulated growth, cancer can form.

Cancer results from mutations that direct a cell to undergo unfettered growth.

One way to kill these tumor cells is to use targeted therapy[8]. Cancer-targeted therapies bind specifically to the defective proteins produced by mutated oncogenes and prevent them from sending a “grow” signal.

Because targeted therapies bind directly to the cancerous protein, they spare most noncancerous cells from being harmed. This results in more specific cancer cell killing and less overall treatment toxicity. In contrast, chemotherapy attacks all actively dividing cells[9], which includes not just cancer but also hair follicles, the digestive tract and other parts of the body.

To make targeted therapies more specific, scientists often study the physical or structural changes that mutations cause in proteins. They design drugs[10] that preferentially bind to these particular changes to prevent the defective protein from causing uncontrolled growth.

However, because mutations can occur in many different areas of a protein[11], multiple targeted therapies are often necessary to bind all the different mutations that occur across cancer types. This leads to a difficult clinical problem: How do physicians match patients to the most effective targeted therapy for their mutations?

Traditional treatments use mutation location

To attempt to answer this question, our research team chose to focus on one oncogene in lung cancer, EGFR[12], or epidermal growth factor receptor. We did this for two reasons. First, lung cancer remains the No. 1 cause[13] of cancer-related deaths worldwide. Second, EGFR mutations are among the most common forms of lung cancer[14] – they occur in approximately a third of non-small-cell lung cancers worldwide[15], amounting to over 550,000 patients annually[16].

EGFR protein structure.
Mutations in EGFR, one of the most commonly mutated oncogenes in lung cancer, change the shape of the protein, which directly affects how it functions. F. Gervasio/UCL Chemistry and ISMB, CC BY[17][18]

EGFR has many different mutations that cause unregulated growth. Multiple generations of targeted therapies[19] are available for this population of patients.

Clinical trials and treatment options for patients with oncogene-driven lung cancer, particularly with EGFR, are currently based on the type[20] and location of the mutation in the DNA[21].

However, mutation location is not the best approach to predict how well patients will respond to a drug. Because mutations change the shape of a protein, they can alter the way targeted therapies interact with the protein[22].

Regrouping cancer mutations

By examining the mutated structures of different EGFR proteins, our team found that they could be categorized into distinct subgroups.

For example, we found that mutations that form away from the areas of the protein that drugs target don’t noticeably affect how well the drug binds to the protein. Cells with this kind of protein mutation were thus killed by all types of EGFR inhibitors. Although these mutations occurred across many locations in the DNA, they shared the same overall structural and functional effect on proteins.

Conversely, mutations that form near typical drug target areas compress this region and prevent certain EGFR inhibitors from attaching to the protein. These mutations also occurred in several different DNA locations.

Pathology slide of lung adenocarcinoma. Targeted therapies hone in on cancerous cells to spare healthy cells from damage. rightdx/iStrock via Getty Images Plus[23]

Based on these findings, our team hypothesized that structural changes in similar protein regions, not DNA location, would cause similar changes in how well a drug works.

To test our hypothesis[24], we retrospectively analyzed public and hospital data on how well patients responded to cancer treatments. We sorted patients into traditional DNA location-based groups and our newly defined structure/function-based subgroups to determine whether one group had more patients who responded better than the other to different drugs.

We found that the structure/function-based subgroups identified nearly twice as many patients that benefited from a particular drug compared with the DNA location-based groups. Grouping patients by structure/function also identified which EGFR inhibitor provided the longest clinical benefit for patients.

More inclusive clinical trials

In addition to potentially matching patients to more effective treatments, clinical trials using structure-based subgroups may lead to broader access to therapies.

Current clinical trials exclude up to a fifth of patients[25] with EGFR mutant non-small-cell lung cancer because each clinical trial typically focuses on only a handful of specific mutation types. Reframing clinical studies to be based on the changes that mutations cause to protein structure and function, as opposed to their location on DNA, could expand treatment options to include patients with more rare EGFR mutant cancers.

This approach provides a framework that clinical trials could use to make studies more inclusive of all types of mutations. And it may also identify previously ignored or hidden mutation subgroups that can lead to additional drug development and ultimately improve patient care.

[Understand new developments in science, health and technology, each week. Subscribe to The Conversation’s science newsletter[26].]

References

  1. ^ many types of cancer treatments (www.cancer.gov)
  2. ^ researches targeted therapies for cancer (scholar.google.com)
  3. ^ recent study (doi.org)
  4. ^ Mutations (www.cancer.gov)
  5. ^ oncogenes (www.cancer.gov)
  6. ^ fetal organ development (doi.org)
  7. ^ general tissue repair and maintenance (doi.org)
  8. ^ targeted therapy (www.cancer.gov)
  9. ^ actively dividing cells (www.cancer.org)
  10. ^ design drugs (doi.org)
  11. ^ many different areas of a protein (doi.org)
  12. ^ EGFR (lcfamerica.org)
  13. ^ No. 1 cause (doi.org)
  14. ^ most common forms of lung cancer (doi.org)
  15. ^ a third of non-small-cell lung cancers worldwide (doi.org)
  16. ^ over 550,000 patients annually (canceratlas.cancer.org)
  17. ^ F. Gervasio/UCL Chemistry and ISMB (commons.wikimedia.org)
  18. ^ CC BY (creativecommons.org)
  19. ^ Multiple generations of targeted therapies (doi.org)
  20. ^ type (doi.org)
  21. ^ location of the mutation in the DNA (doi.org)
  22. ^ alter the way targeted therapies interact with the protein (doi.org)
  23. ^ rightdx/iStrock via Getty Images Plus (www.gettyimages.com)
  24. ^ test our hypothesis (doi.org)
  25. ^ exclude up to a fifth of patients (doi.org)
  26. ^ Subscribe to The Conversation’s science newsletter (theconversation.com)

Read more https://theconversation.com/a-new-way-to-organize-cancer-mutations-could-lead-to-better-treatment-matches-for-patients-168348

Times Magazine

Headless CMS in Digital Twins and 3D Product Experiences

Image by freepik As the metaverse becomes more advanced and accessible, it's clear that multiple sectors will use digital twins and 3D product experiences to visualize, connect, and streamline efforts better. A digital twin is a virtual replica of ...

The Decline of Hyper-Casual: How Mid-Core Mobile Games Took Over in 2025

In recent years, the mobile gaming landscape has undergone a significant transformation, with mid-core mobile games emerging as the dominant force in app stores by 2025. This shift is underpinned by changing user habits and evolving monetization tr...

Understanding ITIL 4 and PRINCE2 Project Management Synergy

Key Highlights ITIL 4 focuses on IT service management, emphasising continual improvement and value creation through modern digital transformation approaches. PRINCE2 project management supports systematic planning and execution of projects wit...

What AI Adoption Means for the Future of Workplace Risk Management

Image by freepik As industrial operations become more complex and fast-paced, the risks faced by workers and employers alike continue to grow. Traditional safety models—reliant on manual oversight, reactive investigations, and standardised checklist...

From Beach Bops to Alpine Anthems: Your Sonos Survival Guide for a Long Weekend Escape

Alright, fellow adventurers and relaxation enthusiasts! So, you've packed your bags, charged your devices, and mentally prepared for that glorious King's Birthday long weekend. But hold on, are you really ready? Because a true long weekend warrior kn...

Effective Commercial Pest Control Solutions for a Safer Workplace

Keeping a workplace clean, safe, and free from pests is essential for maintaining productivity, protecting employee health, and upholding a company's reputation. Pests pose health risks, can cause structural damage, and can lead to serious legal an...

The Times Features

Prefab’s Second Life: Why Australia’s Backyard Boom Needs a Circular Makeover

The humble granny flat is being reimagined not just as a fix for housing shortages, but as a cornerstone of circular, factory-built architecture. But are our systems ready to s...

Melbourne’s Burglary Boom: Break-Ins Surge Nearly 25%

Victorian homeowners are being warned to act now, as rising break-ins and falling arrest rates paint a worrying picture for suburban safety. Melbourne residents are facing an ...

Exploring the Curriculum at a Modern Junior School in Melbourne

Key Highlights The curriculum at junior schools emphasises whole-person development, catering to children’s physical, emotional, and intellectual needs. It ensures early year...

Distressed by all the bad news? Here’s how to stay informed but still look after yourself

If you’re feeling like the news is particularly bad at the moment, you’re not alone. But many of us can’t look away – and don’t want to. Engaging with news can help us make ...

The Role of Your GP in Creating a Chronic Disease Management Plan That Works

Living with a long-term condition, whether that is diabetes, asthma, arthritis or heart disease, means making hundreds of small decisions every day. You plan your diet against m...

Troubleshooting Flickering Lights: A Comprehensive Guide for Homeowners

Image by rawpixel.com on Freepik Effectively addressing flickering lights in your home is more than just a matter of convenience; it's a pivotal aspect of both home safety and en...