Can Cancer Be Designed to "Not Occur/Not Recur": From the Science of Exceptions to Standard Treatment - The Next Generation of Treatment Opened by Cancer "Super Survivors"

Cancer research is now shifting from "why does it develop?" to "why does one survive?" A global initiative is underway to thoroughly investigate "super survivors" who have achieved long-term survival beyond conventional treatment expectations, aiming to uncover hidden "winning strategies" within their bodies and apply these findings to treatment. A feature reported by Undark on August 11 (U.S. time) vividly depicts this forefront. At the center is the French TechBio startup Cure51. Their "Rosalind Study" is a massive project that focuses on the top few percent of long-term survivors of the most formidable cancers, such as pancreatic cancer, extensive-stage small cell lung cancer, and IDH wild-type glioblastoma, comprehensively comparing genetic, tumor, and immune differences. cure51.com

The Power of "Exceptions" in Stories

For example, Yan Bijian, diagnosed with metastatic pancreatic cancer in 2017. Typically, the five-year survival rate for pancreatic cancer does not reach double digits, with stage IV having a harsh reality of only a 1% five-year survival rate. However, he survived due to an "exceptional response" to chemotherapy and now works on the patient committee of the Rosalind Study. He provides tissue samples to understand "why he survived." Johns Hopkins Medicine

Ultimately, Rosalind aims to target a scale of 1,000 cases, meticulously selecting only about the top 3% of long-term survivors. Cure51 has already identified several potential treatment targets by organizing the "biology of survivors" into a global database (details are confidential). However, radiation oncologist Stacey Wentworth expresses concerns about the "temporal constraints of patient aggregation," pointing out the difficulties of past glioblastoma research. Hope and caution coexist.

Animals Teach Us the Blueprint for "Cancer Resistance"

The idea of learning from "exceptions" extends beyond humans. In long-lived bats, mechanisms suggestive of p53 tumor suppressor activation and enhanced immune surveillance have been shown, revealing fragments of physiology that make them less prone to cancer. A 2025 Nature Communications paper reports that while bat fibroblasts can undergo malignant transformation with "just two hits," they exhibit high p53 activity and are prone to apoptosis, suggesting a "paradoxical resistance" strategy similar to the multiple p53 copies in elephants. Nature

Additionally, the naked mole rat possesses a "early contact inhibition" mechanism that physically suppresses proliferation through very high molecular weight hyaluronan (vHMM-HA). In blind mole rats, a "self-destruct mechanism" is triggered, releasing IFN-β to induce mass necrosis when overproliferation is detected. Although direct transplantation to humans may take time, these examples demonstrate that "cancer resistance can be designed." PMCNaturePubMed

Age and Cancer: Why Does It "Decrease" in Old Age?

Cancer increases with age—a common knowledge—but UK statistics show that incidence rates peak at ages 85-89 and then decline in the oldest age groups. A 2024 Nature paper (Tamera et al.) experimentally supports the hypothesis that the decline in cellular "stemness" makes tumors less likely to develop, using the lung as a model. The unexpected pathway involves rewiring iron metabolism to reduce stemness and suppress tumor formation, also suggesting the importance of preventive interventions in youth. Cancer Research UKNature

Risk and DNA Damage: Is There a "Ceiling" Even for Smokers?

It's not just wishful thinking. Single-cell whole-genome analysis of bronchial epithelium shows that the accumulation of somatic mutations due to smoking hits a "ceiling" at around 23 pack-years for some individuals. It's as if a "mutation avoidance system" with individual differences is at work. Such "invisible breakwaters" may also be lurking in the bodies of super survivors. Nature

Tailwinds and Caution: Funding, Clinical Trials, and Ethics

The international Cancer Grand Challenges is promoting the exploration of principles for a "cancer-free body" with large-scale support of up to $25 million, presenting seven challenges including "cancer avoidance" in 2025. Themes that could serve as a foundation for super survivor research, such as AI-human collaboration and tumor microenvironment dynamics, are lined up. Cancer Grand Challenges

On the other hand, voices from the clinical field express concerns about the gap between hype and reproducibility. As a recent topic, the initial results of the "off-the-shelf vaccine" ELI-002 2P targeting KRAS mutations were reported by The Guardian. It showed promising immune responses in suppressing recurrence of pancreatic and colorectal cancer, but the scale is small, and control groups are limited. While there is hope, it is necessary to calmly await the results of the next phase of trials. The Guardian

The Rumblings of Social Media—Hope, Caution, and Voices of Those Involved

Browsing social media, three major "rumblings" can be heard.

1. Hope of Those Involved
   In the cancer community, posts sharing long-term survival from stage IV and "living normally even during treatment" create relief and solidarity. Threads where the short phrase "Keep the faith" is repeated are symbolic. There is hope that the accumulation of exceptions will create a "new standard." Reddit

2. Clinical Trials Are Key
   On X (formerly Twitter), the straightforward opinion that "ultimately, clinical trials are everything for treatment" is repeatedly shared. It is pointed out that proper trial design and long-term follow-up are crucial, without being overly swayed by the narrative of research. X (formerly Twitter)

3. Cautious Field Sensibility
   While the ambition of the Rosalind Study is appreciated, concerns about the hurdles of patient recruitment and timelines are also discussed. Comments from Dr. Wentworth, introduced by Undark, reflect the field's awareness of the "difficulty of gathering." Undark Magazine

How to Move Forward

The "secrets of super survivors" do not lie in a single magic bullet but appear to be a bundle of multiple small advantages. Genetic chance, immune tuning, the delicate balance of tumors and their surrounding environment, and life history. Three implementations can be derived from this.

• Redesign of Selection and Stratification: Database patterns of the top few percent of responders and optimize treatment selection by translating them into biomarkers. This is precisely what Rosalind aims for. cure51.com

• Reflecting "Resistance" in Organisms: Learn from the cancer resistance of bats and moles, and pharmacologically or through vaccines, recreate "breakwaters" such as p53 pathways and extracellular matrix control. NaturePMC

• Revisiting Preventive Age: If age-related changes in stemness affect the seeding of cancer, place more emphasis on intervention design from a young age (smoking cessation support, infection control, reduction of environmental factors, preventive vaccines). Nature

Of course, handling data (privacy, ownership, transparency of utilization), reproducibility of results, and cost-effectiveness verification are indispensable. However, if "exceptions" can be systematized, the quality of standard treatment will quietly be elevated. Super survivors are not stories of miracles. They are the next blueprint for clinical practice. Undark Magazine

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