From Poison to Precision in the Century-Long Fight Against Cancer
A hundred-year transformation from toxic poisons to mRNA vaccines and AI-powered diagnostics
Imagine a medical journey that began with toxic poisons and radical surgeries and has now arrived at mRNA vaccines and AI-powered diagnostics. This extraordinary evolution defines the first centennial of cancer science—a hundred-year transformation that has fundamentally changed how we understand, detect, and treat one of humanity's most complex diseases. The field of oncology has progressed from a one-size-fits-all approach using blunt tools to an era of precision medicine where treatments are tailored to individual genetic profiles and specific cancer characteristics.
Throughout this century, our perception of cancer has undergone several paradigm shifts—from viewing it as purely a disease of uncontrolled cell division to understanding the crucial role of the immune system, metabolic pathways, and cellular microenvironments.
The past decade alone has witnessed unprecedented advances, with 2025 emerging as a landmark year showcasing the tangible results of a century of accumulated knowledge. As we stand at this hundred-year milestone, we can see how foundational discoveries have paved the way for today's revolutionary approaches, turning what was once almost universally fatal into increasingly manageable—and in some cases, curable—conditions.
The earliest systematic cancer treatments emerged from the observation that mustard gas compounds could suppress bone marrow activity during World War I. This led to the development of the first chemotherapeutic agents, which worked on the simple principle of killing rapidly dividing cells—both cancerous and healthy.
Parallel to drug development, radiation therapy evolved from crude applications to highly targeted approaches using three-dimensional conformal radiation and intensity-modulated radiation.
The discovery of DNA's structure in 1953 unleashed a transformative wave in cancer science. Researchers began identifying specific genetic mutations and signaling pathways that drive cancer development.
The concept of harnessing the immune system to fight cancer dates back to the 1890s with William Coley's toxins, but only in recent decades has it become a clinical reality with the success of immune checkpoint inhibitors.
| Time Period | Dominant Paradigm | Key Advancements |
|---|---|---|
| 1920s-1950s | Cytotoxic Chemotherapy | First nitrogen mustard agents; Antifolate drugs |
| 1960s-1980s | Combination Chemotherapy | Drug combinations; Adjuvant chemotherapy |
| 1990s-2010s | Targeted Therapy | Monoclonal antibodies; Small molecule inhibitors |
| 2010s-Present | Immunotherapy & Precision Medicine | Checkpoint inhibitors; CAR-T cells; Biomarker-guided therapy |
| Present-Future | AI-Integrated Approaches | Predictive algorithms; Digital pathology; Computational drug discovery |
Visualization of treatment impact across different eras of cancer science
Cancer immunotherapy continues to evolve beyond initial approaches, with 2025 witnessing significant progress. The Cancer Research Institute recognized foundational contributors to this field 2 .
AI technologies are now revolutionizing every aspect of cancer science. DeepHRD, a deep-learning tool developed in 2025, can detect homologous recombination deficiency with up to three times more accuracy 7 .
2025 has introduced first-in-class treatments with entirely new mechanisms of action. BNT142 represents the first clinical proof-of-concept for an mRNA-encoded bispecific antibody 6 .
| Therapy/Technology | Cancer Type | Mechanism of Action | Development Stage | Key Finding |
|---|---|---|---|---|
| DTP Combination (Pembrolizumab + Dabrafenib + Trametinib) | Anaplastic Thyroid Cancer with BRAF V600E mutation | Neoadjuvant targeted therapy + immunotherapy followed by surgery | Phase II Trial | 66% of patients had no residual cancer; 69% 2-year survival |
| BNT142 (mRNA-encoded bispecific antibody) | CLDN6-positive tumors (testicular, ovarian, NSCLC) | Lipid nanoparticle delivery of mRNA encoding anti-CLDN6/CD3 bispecific antibody | Phase I/II Trial | First proof-of-concept for mRNA-encoded bispecific antibody; Manageable safety profile |
| DeepHRD AI Tool | Various cancers with homologous recombination deficiency | Deep learning analysis of standard biopsy slides | Retrospective Validation | 3x more accurate than genomic tests; <5% failure rate vs. 20-30% with current tests |
| VLS-1488 (KIF18A inhibitor) | Cancers with chromosomal instability | Oral inhibitor of kinesin protein required for division of unstable cancer cells | Phase I/II Trial | Generally safe and tolerable with early anti-tumor activity |
| Pivekimab Sunirine (PVEK) | Blastic plasmacytoid dendritic cell neoplasm (BPDCN) | Antibody-drug conjugate targeting CD123 (IL-3Rα) | Phase II Trial | High and durable complete remission responses; FDA approval sought |
Anaplastic thyroid cancer with BRAF V600E mutations represents one of the most aggressive and treatment-resistant malignancies, typically diagnosed at advanced stages when surgical removal is often impossible. Before recent advances, prognosis was extremely poor, with conventional approaches offering limited benefit.
This dire situation provided the impetus for a groundbreaking Phase II clinical trial presented at the 2025 ASCO Annual Meeting by researchers from MD Anderson Cancer Center 6 . The trial tested a novel neoadjuvant approach—using targeted therapy and immunotherapy before surgery—to shrink tumors and enable more successful surgical outcomes.
Researchers enrolled patients with Stage IV BRAF V600E-mutated anaplastic thyroid cancer, all of whom had disease that was initially considered inoperable.
Patients received the DTP combination—dabrafenib (BRAF inhibitor), trametinib (MEK inhibitor), and pembrolizumab (anti-PD-1)—prior to surgery.
Following neoadjuvant treatment, patients underwent surgery to remove any remaining cancer tissue.
Researchers evaluated pathological responses by measuring the percentage of patients achieving a complete pathological response.
| Outcome Measure | Result |
|---|---|
| Complete Pathological Response | 66% of patients |
| Two-Year Overall Survival | 69% |
| Successful Surgical Resection | Significantly increased |
| Treatment-Related Adverse Events | Manageable profile |
The trial results, published in 2025, demonstrated remarkable success. An unprecedented 66% of patients achieved a complete pathological response with no residual anaplastic thyroid cancer detected in their surgical specimens after DTP treatment 6 . This translated into a two-year survival rate of 69%, dramatically higher than the historical average of approximately 20% with conventional treatments.
The findings strongly indicate that neoadjuvant DTP treatment enables higher rates of successful surgical resection by substantially shrinking tumors before operation.
The scientific importance of these results extends beyond anaplastic thyroid cancer specifically. This trial exemplifies the broader shift in cancer treatment paradigms toward three key principles: the use of neoadjuvant (pre-surgical) approaches for advanced cancers, the power of rational combination therapies targeting multiple pathways simultaneously, and the importance of biomarker-driven patient selection.
| Treatment Approach | Complete Response Rate | 2-Year Survival | Surgical Resectability | Key Limitations |
|---|---|---|---|---|
| Conventional Chemotherapy | <10% | ~20% | Limited | High toxicity, limited efficacy |
| Single-Agent Targeted Therapy | 10-15% | 30-40% | Moderate | Rapid development of resistance |
| DTP Combination (2025 Trial) | 66% | 69% | Significantly enhanced | Specific to BRAF V600E mutation |
Modern cancer research relies on sophisticated tools and technologies that have evolved dramatically throughout the history of cancer science.
Identify mutations, biomarkers, and therapeutic targets; Guide precision medicine approaches
2025 Development: DeepHRD - AI-powered analysis of standard biopsy slides for HRD detection 7
Enable development of targeted immunotherapies with specific cancer cell targeting
2025 Development: Lynozyfic (bispecific antibody for multiple myeloma) 7
| Tool Category | Specific Examples | Function in Cancer Research | 2025 Developments |
|---|---|---|---|
| Genomic Sequencing Technologies | Next-Generation Sequencing (NGS), Whole Exome/Genome Sequencing | Identify mutations, biomarkers, and therapeutic targets; Guide precision medicine approaches | DeepHRD: AI-powered analysis of standard biopsy slides for HRD detection 7 |
| AI and Computational Resources | Prov-GigaPath, MSI-SEER, HopeLLM, NCI-DOE Collaboration Tools | Enhance diagnostic accuracy, predict treatment outcomes, streamline clinical trials 7 8 | HopeLLM platform for summarizing patient histories and identifying clinical trial matches 7 |
| Research Data Platforms | NCI Cancer Research Data Commons, Human Tumor Atlas Network | Provide comprehensive multimodal datasets for analysis and algorithm training 8 | Expansion of HTAN Data Portal with 3D tumor atlases 8 |
| Immunotherapy Reagents | Bispecific Antibodies, CAR-T Constructs, Antibody-Drug Conjugates | Enable development of targeted immunotherapies with specific cancer cell targeting | Lynozyfic (bispecific antibody for multiple myeloma) 7 |
| Model Systems | Patient-Derived Organoids, Genetically Engineered Mouse Models | Provide physiologically relevant systems for testing therapies before human trials | Improved organoid cultures for therapy response prediction |
| Diagnostic Biomarkers | CLDN6, HRD Signatures, MSI-H Status | Identify patient populations likely to respond to specific targeted therapies | CLDN6 as target for BNT142 mRNA therapy 6 |
The field is increasingly focusing on intervening before cancer develops in high-risk individuals. The National Cancer Institute's Division of Cancer Prevention is championing this approach through research on "interception of the carcinogenesis process before invasive cancer develops" 9 .
Artificial intelligence will continue to transform cancer science, though researchers must address significant challenges including "the need for large, high-quality datasets, variability in imaging quality, difficulties integrating AI tools into clinical workflows" 7 .
The integration of technological approaches will likely define the next era of cancer science. Future treatments will increasingly combine modalities—such as pairing targeted therapies with immunotherapies—to overcome resistance mechanisms and improve outcomes.
The centennial of cancer science tells a remarkable story of evolution—from the first crude cytotoxic chemicals to today's sophisticated molecular-targeted therapies and immunotherapies. This hundred-year journey has transformed cancer from a nearly universally fatal diagnosis to a set of diseases that we are increasingly learning to manage effectively, and in many cases, cure.
The breakthroughs of 2025—from mRNA-encoded bispecific antibodies to AI-powered diagnostics—demonstrate how foundational discoveries have paved the way for today's revolutionary approaches.
As cancer science enters its second century, the field continues to accelerate at an unprecedented pace. The convergence of immunotherapy, artificial intelligence, and precision medicine creates a powerful synergy that promises to further improve cancer outcomes while reducing treatment side effects.
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