Why Insulin Resistance Predicts Cancer Outcomes Better Than Staging (2026)

By Editorial Team

Cancer staging tells us where the tumor is. Insulin resistance tells us what kind of body the tumor is growing in.

Modern oncology places enormous faith in staging systems. TNM categories, AJCC groupings, and increasingly granular molecular subtypes are used to estimate prognosis, guide treatment, and reassure patients.

Yet clinicians and patients alike encounter a persistent paradox:

Two patients. Same cancer. Same stage. Same treatment. Radically different outcomes.

Staging explains part of the story — but not nearly enough. A growing body of evidence suggests that host metabolic health, particularly insulin resistance, often predicts outcomes more reliably than tumor stage alone.

This is not an argument against staging. It is an argument that staging is incomplete.

What Cancer Staging Measures — and What It Ignores

Cancer staging excels at describing tumor geography:

  • Tumor size

  • Lymph node involvement

  • Distant spread

What it largely ignores:

  • Insulin and glucose dynamics

  • Inflammatory tone

  • Immune competence

  • Hormonal signaling

  • Energy availability

Staging answers the question:

“How far has this cancer progressed anatomically?”

It does not answer:

“How supportive is this biological environment for cancer survival, adaptation, and recurrence?”

That second question matters more than most models admit.

TyG index

Insulin Resistance Is Not a Metabolic Side Issue

Insulin resistance is often framed as a pre-diabetic inconvenience — a blood sugar problem to be managed later.

Biologically, it is something else entirely.

Insulin resistance represents a chronic pro-growth, pro-survival signaling state, characterized by:

  • Persistent hyperinsulinemia

  • Increased IGF-1 signaling

  • Elevated glucose and lipid flux

  • Suppressed autophagy

  • Low-grade systemic inflammation

From the perspective of cancer biology, this is not a neutral background condition.

It is a fertile ecosystem.

Cancer Cells Exploit Insulin-Resistant Environments

Cancer cells are opportunists. They do not need ideal conditions — only favorable ones.

Insulin-resistant hosts provide:

  • Abundant circulating glucose (Warburg advantage)

  • Continuous anabolic signaling

  • Reduced metabolic stress

  • Impaired immune surveillance

  • Easier angiogenic support

In contrast, metabolically healthy hosts impose:

  • Nutrient competition

  • Energy scarcity signals

  • Stronger immune pressure

  • Higher oxidative and metabolic stress

Put simply:

Insulin resistance lowers the energetic and immunologic cost of being cancer.

Staging does not capture this advantage. Metabolic state does.

Why Outcomes Diverge Within the Same Stage

Across cancer types — breast, colorectal, pancreatic, prostate, lung — a consistent pattern emerges:

Patients with:

  • Type 2 diabetes

  • Prediabetes

  • Central obesity

  • NAFLD

  • Hyperinsulinemia

Experience:

  • Higher recurrence rates

  • Reduced treatment response

  • Shorter progression-free survival

  • Lower overall survival

This remains true after adjusting for stage.

In real-world practice, insulin resistance often explains outcome variability that staging cannot.


Insulin Resistance as the Missing Prognostic Variable

Cancer staging remains the dominant language of oncology. TNM classification determines treatment pathways, trial eligibility, and survival estimates. Yet staging answers only one question: how far the tumor has spread.

It does not answer a more consequential one:
what biological environment the tumor is growing in.

Insulin resistance is increasingly that missing variable.

Across multiple cancer types, insulin-resistant patients experience poorer outcomes at the same stage, receive the same treatments, and yet diverge dramatically in survival, recurrence, and treatment response. This divergence persists even after adjusting for BMI, diabetes status, and traditional metabolic markers.

The implication is uncomfortable but clear: stage alone is not prognostic enough.

Why Insulin Resistance Outperforms Stage in Real-World Outcomes

Insulin resistance is not merely a comorbidity—it is a systemic growth signal.

Chronically elevated insulin and glucose availability:

  • Activate PI3K–AKT–mTOR signaling

  • Promote cancer stem cell survival

  • Suppress apoptosis

  • Impair immune surveillance

  • Increase resistance to cytotoxic stress

Two patients may both be Stage II or Stage III on paper, but biologically they are not equivalent. One enters treatment in a relatively neutral metabolic state; the other in a persistently anabolic, pro-inflammatory, immune-suppressive environment.

Staging cannot distinguish between these states.
Insulin resistance can.

The TyG Index: Making Insulin Resistance Measurable

If insulin resistance predicts outcomes better than stage, the next question becomes practical: how do we measure it reliably?

This is where the Triglyceride–Glucose (TyG) index becomes central.

TyG is calculated from two routine fasting labs—triglycerides and glucose—and serves as a validated surrogate marker of insulin resistance. Unlike fasting insulin or HOMA-IR, it is:

  • Widely available

  • Inexpensive

  • Reproducible

  • Validated across populations

  • Suitable for retrospective and population-level studies

Crucially, TyG identifies high-risk metabolic states before diabetes develops, and often in patients with “normal” fasting glucose and acceptable BMI.

In cancer cohorts, elevated TyG has been associated with:

  • Worse overall and cancer-specific survival

  • Higher recurrence rates

  • Reduced chemotherapy sensitivity

  • Inferior immunotherapy responses

These associations frequently remain significant after adjustment for tumor stage.

Staging Describes Anatomy. TyG Describes Terrain.

Tumor stage is static.
Insulin resistance is dynamic.

Staging captures the geography of disease.
TyG captures the terrain in which disease evolves.

This distinction helps explain several persistent clinical paradoxes:

  • Why some early-stage cancers recur unexpectedly

  • Why some advanced cancers progress slowly

  • Why lifestyle and metabolic interventions can alter outcomes even late in disease

  • Why guideline-concordant care yields wildly different results between patients

These observations strain staging-based explanations but align naturally with a metabolic framework.

Why TyG Often Beats BMI, Diabetes Labels, and Glucose Alone

Traditional metabolic categories fail oncology patients:

  • BMI cannot distinguish metabolically healthy from metabolically toxic states

  • Diabetes diagnoses arrive late in the disease process

  • Fasting glucose misses compensatory hyperinsulinemia

TyG integrates lipid overflow and glucose dysregulation into a single signal that more accurately reflects the insulin-resistant state driving tumor behavior.

In multiple population studies, TyG predicts cancer incidence and mortality independently of—and sometimes more strongly than—these conventional markers.

In practical terms, TyG identifies risk where staging and standard metabolic labels are silent.


Insulin Resistance Actively Undermines Cancer Therapy

The problem is not only cancer growth. It is treatment resistance.

Insulin resistance:

  • Activates PI3K–AKT–mTOR survival pathways

  • Promotes chemotherapy resistance

  • Blunts radiotherapy sensitivity

  • Reduces T-cell activation and infiltration

  • Impairs immunotherapy efficacy

A tumor can shrink on imaging while the underlying metabolic environment quietly prepares it for rebound.

Staging celebrates response. Metabolism predicts durability.

Cancer Stem Cells and the Metabolic Escape Problem

Cancer stem cells (CSCs) are increasingly recognized as drivers of:

  • Relapse

  • Metastasis

  • Treatment failure

These cells are:

  • Metabolically flexible

  • Stress resistant

  • Capable of dormancy

Insulin-resistant environments:

  • Reduce metabolic bottlenecks

  • Provide continuous fuel access

  • Favor dormancy-then-reactivation cycles

This helps explain why:

  • “Successful” treatments fail long-term

  • Recurrences are often more aggressive

  • Later-stage disease is harder to control

Staging cannot detect this biology. Metabolic context often predicts it.

Why Guidelines Lag Behind the Science

If insulin resistance is so important, why is it barely mentioned in oncology guidelines?

Three structural reasons:

  1. Staging is discrete; metabolism is continuous
    Guidelines favor clean categories over messy gradients.

  2. No single specialty owns metabolic health
    Oncology treats tumors, not insulin signaling.

  3. There is little commercial incentive
    No blockbuster drug is built around restoring metabolic resilience.

As a result, metabolic health is relegated to “lifestyle advice” — despite its prognostic weight.

A More Honest Prognostic Model

A more realistic framework looks like this:

Cancer outcome = tumor biology × host metabolic environment

Staging captures tumor extent well. Insulin resistance captures much of the host environment.

Ignoring either produces false confidence.

If insulin resistance predicts outcomes better than stage, then staging alone is an incomplete decision-making tool.

More importantly, insulin resistance is modifiable. Tumor stage cannot be reversed. TyG can change.

Dietary interventions, physical activity, insulin-lowering strategies, metabolic therapies, and lifestyle restructuring can shift the metabolic environment—even in patients with advanced disease.

This reframes cancer care:

  • Not as a static battle against tumor burden

  • But as a dynamic contest between tumor biology and host metabolism

Staging tells us how advanced the cancer is.
TyG helps tell us how likely it is to resist, recur, or respond.

That distinction may explain why insulin resistance increasingly outperforms stage as a predictor of real-world outcomes.

The Shift Is Already Happening — Quietly

This metabolic reframing is not fringe. It is emerging, cautiously, across the literature:

  • Survival advantages associated with metformin use

  • Fasting-mimicking diet trials

  • Obesity-adjusted immunotherapy analyses

  • Insulin resistance as a modifier of treatment response

The language remains conservative. The implications are not.

The Bottom Line

Cancer staging tells us how advanced the disease appears. Insulin resistance tells us how permissive the terrain is.

As long as oncology treats metabolic health as a footnote rather than a core variable, prognosis will remain incomplete — and outcomes will continue to surprise both patients and clinicians.

Understanding cancer requires looking beyond the tumor. It requires understanding the body it inhabits.

FAQ

How does insulin resistance affect cancer risk?

It has to do with fat, especially the fat around your waist and organs. If you are insulin resistant, you are more likely to create fat cells and not be able to break down fat cells. The resulting weight gain, inflammation and hormone disruptions raise your risk for up to 13 types of cancer.

Independent of weight, insulin increases cell production and reduces cell death. That means there is more opportunity for something to go wrong and cancer to develop. Long-term increased insulin raises your risk for breast, prostate and colorectal cancers. There are really good studies that show that changing your lifestyle habits, including eating well, staying active and maintaining a healthy weight, really decreases that risk for those three cancers.

What can you do to prevent insulin resistance and related cancers?

You can prevent and even reverse insulin resistance through weight management, exercise and healthy food choices. These steps will help you stabilize your insulin and blood sugar and reduce inflammation.
  • Reduce body fat. Losing just 10% of your body weight directly correlates with improved health. That includes insulin resistance, diabetes and hypertension. If you lose 10% of your body weight, you’ll see major improvement with all of those chronic conditions.
  • Get and stay physically active. Aim for at least 150 minutes of moderate exercise or 75 minutes of vigorous exercise each week, and practice strength training at least twice a week. Even if you don’t lose any weight, physical activity will help you stabilize your blood sugar and insulin.
  • Eat a plant-based diet that is low in added sugar and saturated fat. Your diet really matters when it comes to trying to fight inflammation and manage your blood sugar and insulin. You want your body in the state where it’s not like a match, burning everything up. You want it to be in a state where it’s happy. It likes that water. It likes those veggies.

Does insulin resistance increase TNBC aggressiveness?

Insulin resistance is linked to increased aggressiveness in triple-negative breast cancer (TNBC) due to metabolic changes that promote tumor growth and spread. This connection highlights the need for tailored treatments for patients with obesity-driven diabetes to improve their outcomes. (eCancer.org 2025)

Does insulin resistance cause pancreatic cancer?

Insulin itself does not directly cause pancreatic cancer, but high insulin levels and insulin resistance are linked to an increased risk of developing the disease. This relationship is thought to involve the overstimulation of pancreatic cells, which can lead to inflammation and potentially precancerous changes. (Frontiersin.org 2022)

Editorial Note and Disclaimer

This article discusses associations and biological mechanisms, not individualized medical advice. Cancer care decisions should always be made with qualified clinicians, integrating tumor characteristics, patient health, and evolving evidence.

Comments

Post a Comment

Popular posts from this blog

Ivermectin for Cancer Treatment: Protocols and Evidence (2025 Edition)

By Editorial Team
Image
Ivermectin, a drug primarily used to treat parasitic infections, has gained attention for its potential anti-cancer properties, particularly in alternative treatment protocols. Popularized by figures like Dr. William Makis, these protocols combine ivermectin with supplements and lifestyle changes to target aggressive cancers. This article explores the science, protocols, case reports, risks, and controversies surrounding ivermectin’s use in cancer treatment, providing a balanced guide for readers. What is the Ivermectin Cancer Protocol? Ivermectin cancer protocols, notably those developed by Dr. William Makis, combine ivermectin with supplements like curcumin, vitamin D, and berberine, alongside dietary and lifestyle changes. These protocols are tailored to cancer severity, with higher doses recommended for aggressive cases. The term “turbo cancers,” used by some proponents, refers to rapidly progressing cancers, though it is not a standard medical term and lacks clear scientific defin...
Read more

Exploring Ivermectin, Mebendazole and Fenbendazole as Aggressive Cancer Treatments: Research, Protocols, and Controversies (2025)

By Editorial Team
Image
Fenbendazole and ivermectin, both antiparasitic drugs that have shown potential in cancer treatment through several mechanisms, such as slowing cancer cell growth and boosting the immune response. Fenbendazole is being studied for its ability to disrupt energy production in cancer cells, effectively hindering their growth. Ivermectin, on the other hand, has been explored in combination with checkpoint inhibitors to boost the immune system's response to tumors—especially in challenging cases like triple-negative breast cancer. Introduction Cancer remains a leading cause of morbidity and mortality worldwide, with an increasing incidence of aggressive and treatment-resistant tumors such as triple-negative breast cancer (TNBC), pancreatic adenocarcinoma, and glioblastoma. Despite significant advances in targeted therapies and immunotherapies, many patients continue to face limited effective options, highlighting an urgent need for novel, affordable, and accessible treatment strategies....
Read more

Fenbendazole and Ivermectin for Cancer: A Case Series of Over 360 Patients (2026)

By Editorial Team
Image
Anecdotal reports and preliminary studies suggest that ivermectin and fenbendazole, both antiparasitic drugs, may have potential anticancer effects when used alongside other treatments.  Many people immediately dismiss the potential of ivermectin and fenbendazole when they learn it is “horse or dog medicine”. That initial reaction is overcome when genuine human success stories are told including the lack of serious side effects. The testimonials you are about to read are from individuals who have bravely shared their experiences in the hope of inspiring and uplifting others. These are raw human accounts, unfiltered by gatekeepers—not peer-reviewed studies—but they offer insights that may be valuable to those searching for options. However, we acknowledge that robust clinical trials are needed to provide more conclusive scientific evidence. Contents: Editor's Preface Introduction Fenbendazole and Ivermectin Case Series Compilation (alphabetical) Breast Cancer Success Stories  (...
Read more

Fenbendazole and the Joe Tippens Protocol: Evidence, Risks, and Current Perspective (2026 Update)

By Editorial Team
Image
Introduction The Joe Tippens Protocol revolves around the off-label use of fenbendazole (a veterinary dewormer commonly sold as Panacur C or Safe-Guard) combined with various supplements for cancer. Joe Tippens popularized this approach after claiming it contributed to his remission from metastatic small-cell lung cancer in 2017. As of 2025, Joe Tippens remains alive and reports being cancer-free for over 8 years, continuing a maintenance version of the protocol. Fenbendazole is marketed for animals (e.g., Panacur C, Safe-Guard ) and has no regulatory approval for human cancer treatment . Evidence for anticancer effects is primarily preclinical or anecdotal , and clinical trials in humans are lacking. Important Disclaimer: Fenbendazole is not approved by the FDA, EMA, or any regulatory body for human use or cancer treatment. There are no completed randomized controlled human clinical trials demonstrating its safety or efficacy against cancer. All human evidence is anecdotal, from case...
Read more

Fenbendazole vs Ivermectin for Cancer: Differences and Which Is Better?

By Editorial Team
Image
Cancer patients are increasingly inquiring about the use of the anthelmintic drugs Fenbendazole (FenBen) and Ivermectin (IVM) as potential treatments for cancer. Notably, these patients typically fall into two distinct groups, neither of which represents the usual stage 1 or 2 cancer cases where conventional therapies often show promise. The first group consists of older men whose lung or prostate cancer has recurred. Having undergone conventional treatments previously without success, they express skepticism about its effectiveness this time around. The second, larger group comprises younger patients under 40 dealing with aggressive breast cancer, colorectal cancer, or lymphoma—forms of early-onset cancers that appear to lack the typical mutations observed in traditional cases. This article aims to delve into the differences between Fenbendazole and Ivermectin by examining their me...
Read more

Top 10 Cancer Fighting Supplements: Evidence Based Literature Review (2025)

By Editorial Team
Image
Are you overwhelmed by conflicting advice on cancer, diet, and supplements ? You’re not alone. With so many claims out there, it’s hard to separate fact from fiction . Can certain foods lower your cancer risk ? Are some foods increasing it without you realizing? What about vitamin and mineral supplements —do they help prevent cancer, or could they actually increase your risk ? The term " anti-cancer supplements " can be misleading. While some nutrients support the body in cancer prevention or treatment, others may interfere with therapies or even pose risks. There are presently over 1,500 herbs and food supplements in commerce, many of them with claims in use against cancer. This guide compiles over 500 scientific r...
Read more

Fact Check: Can Ivermectin and Fenbendazole Help Treat Cancer?

By Editorial Team
Image
Ivermectin and fenbendazole, originally developed as antiparasitic drugs, are sparking hope in the fight against cancer, fueled by inspiring stories like those shared by actor  Mel Gibson on The Joe Rogan Experience , where he celebrated friends’ remarkable recoveries. While these medications aren’t yet standard cancer treatments, early research is uncovering exciting potential. Scientists are encouraged by promising lab studies and are calling for more clinical trials to confirm their effectiveness and ensure safe use in humans, paving the way for innovative, accessible therapies that could transform lives. Introduction and Context According to a January 22, 2025 fact-check article by AFP: "The anti-parasitic drugs ivermectin and fenbendazole are not currently recommended for cancer, but posts spread across social media touting the medications after actor  Mel Gibson claimed on the Joe Rogan Experience  that they cured his friends' cases of the disease. Oncology ex...
Read more

Fenbendazole and Cancer: What the Science Really Shows (Evidence, Risks & Open Questions)

By Editorial Team
Image
Abstract Background:  Fenbendazole (FBZ), a benzimidazole anthelmintic approved for veterinary use, has attracted attention for potential anticancer activity based on laboratory findings and widespread anecdotal reports.  Objective:  To critically appraise the current evidence on fenbendazole and cancer using a peer‑review style framework.  Methods:  Narrative review of preclinical studies, publicly reported human case narratives, and safety signals, with emphasis on evidence hierarchy and translational limitations.  Results:  Preclinical data demonstrate antiproliferative effects via microtubule disruption and metabolic stress in vitro and in animal models. Human evidence is limited to uncontrolled case reports; no Phase I–III clinical trials or regulatory approvals for oncology exist. Safety data in humans are sparse, with hepatotoxicity signals reported.  Conclusions:  Fenben...
Read more

Best Fenbendazole Dosage for Cancer in Humans: Benefits, Risks, and Guidelines (2025)

By Editorial Team
Image
What is Fenbendazole? Fenbendazole is a broad spectrum anti-parasitic used against gastrointestinal parasites including: giardia, roundworms, hookworms, whipworms, the tapeworm genus Taenia (but not effective against Dipylidium caninum, a common dog tapeworm), pinworms, aelurostrongylus, paragonimiasis, strongyles, and strongyloides that can be administered to sheep, cattle, horses, fish, dogs, cats, rabbits, most reptiles, freshwater shrimp tanks as planaria and hydra treatments, as well as seals. (2) Fenbendazole, has garnered ⁤attention​ for its potential use ​in‍ humans.‍ The Fenbendazole Cancer Protocol gained rapid interest over the past years following some  fenbendazole advanced cancer success stories . Joe Tippens founded the protocol  after he was told a story about a scientist at Merck Animal Health that had been performing cancer research on mice. The research included injecting different types of cancers into different mice body parts. The scientists discover...
Read more

2025 Study: Ivermectin and Balstilimab for Stage 4 Triple Negative Breast Cancer - Cedars-Sinai Medical Center Study

By Editorial Team
Image
Authors: Yuan Yuan, Jin Sun Bitar, MaLia Walker, David Lin, January Lee, So Yung Choi, Stephen Shiao, Mourad Tighiouart, Paul H. Frankel, Peter P. Lee Affiliation: Cedars-Sinai Medical Center, Los Angeles, CA Abstract e13146  (2025 ASCO Annual Meeting) is a phase 1/2 study of ivermectin in combination with balstilimab after 1-2 prior lines of therapy for triple negative breast cancer Background: Despite recent FDA approval of immune checkpoint inhibitor (ICI) and antibody-drug conjugates (ADCs), therapeutic options for metastatic triple negative breast cancer (mTNBC) remain limited. Preclinical data showed that ivermectin induces robust T cell infiltration into breast tumors and turning “cold” tumors “hot” in mouse model of TNBC. Balstilimab is a fully humanized IgG4 anti-PD-1 agent with proven safety and efficacy in metastatic cervical cancer. The current phase I/II trial is designed to test the safety and efficacy of the combination of ivermectin and balstilimab in patients wit...
Read more