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Cited by 491Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesCancer Cells and Metastasis

Analyses of repeated failures in cancer therapy for solid tumors: Poor tumor-selective drug delivery, low therapeutic efficacy and unsustainable costs

Open access
Maeda, Hiroshi, Khatami, Mahin·2018·Clinical and Translational Medicine
DOI 10.1186/s40169-018-0185-6PMC PMC5852245
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Abstract

For over six decades reductionist approaches to cancer chemotherapies including recent immunotherapy for solid tumors produced outcome failure-rates of 90% (±5) according to governmental agencies and industry. Despite tremendous public and private funding and initial enthusiasm about missile-therapy for site-specific cancers, molecular targeting drugs for specific enzymes such as kinases or inhibitors of growth factor receptors, the outcomes are very bleak and disappointing. Major scientific reasons for repeated failures of such therapeutic approaches are attributed to reductionist approaches to research and infinite numbers of genetic mutations in chaotic molecular environment of solid tumors that are bases of drug development. Safety and efficacy of candidate drugs tested in test tubes or experimental tumor models of rats or mice are usually evaluated and approved by FDA. Cost-benefit ratios of such 'targeted' therapies are also far from ideal as compared with antibiotics half a century ago. Such alarming records of failure of clinical outcomes, the increased publicity for specific vaccines (e.g., HPV or flu) targeting young and old populations, along with increasing rise of cancer incidence and death created huge and unsustainable cost to the public around the globe. This article discusses a closer scientific assessment of current cancer therapeutics and vaccines. We also present future logical approaches to cancer research and therapy and vaccines.

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  • Other mechanical pressures and physical barriers due to rapid growth of tumor mass may contribute to heterogeneity of the EPR effect and declined efficiency of nanotherapeutics in human tumors.

    “The other mechanical pressures and physical barriers due to the rapid growth of tumor mass may also contribute to the heterogeneity of the EPR effect and declined efficiency of nanotherapeutics in human tumors [103].”

    From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [103]

    In “Problems with cancer drug screening and safety in rats and mice” (page unavailable), the paper describes growth-induced physical pressure as an artifact of rapidly growing mouse tumors, not a feature comparable to human tumor growth. It says human tumors usually grow much more slowly. This runs contrary to the claim’s proposed rapid-growth pressure mechanism in human tumors; the passage does not assess its proposed effect on EPR heterogeneity. (LLM, conf=0.84)

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Research works printed but not linked: 6

  1. [8]International Agency for Research on Cancer (IARC) (2014) WHO, Press Release, Lyon/London, 3 February
  2. [76]Jacobs JGL Snackey C Geldof AA Characiejus D Moorselaar RJAV Otter WD Inefficacy of therapeutic cancer vaccines and proposed improvements. Casus of prostate cancer Anticancer Res 2014 34 2689 2700 24922629
  3. [100]Maeda H, Sato K, Akaike T (1995) Superoxide radical generation from heterocyclic amines. In: Proceedings of the 23rd International Symposium of the Princess Takamatsu Cancer Research Fund. Heterocyclic amines in cooked foods: possible human carcinogens (Adamson RH, Gustafsson JA, Ito N, Nagao M, Sugimura T, Wakabayashi K, Yamazoe Y (eds)) Princeton Scientific Publishing Co., New Jersey, p. 103–112
  4. [103]Maeda H (2011) Enhanced permeability and retention effect in relation to tumor targeting. In: Kratz F, Senter P Steinhagen H (eds). Drug delivery in oncology. From basic research to cancer therapy, Vol. 1. Wiley, Weinheim, pp 65–84
  5. [126]Brill S Bitter pill: why medical bills are killing us 2013 Florida Time (USA edition) 16 55
  6. [144]Maeda H Macromolecular therapeutics in cancer treatment: the EPR effect and beyond J Control Release 2012 164 138 144 10.1016/j.jconrel.2012.04.038 22595146 · DOI

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Authors
Maeda, H., & Khatami, M.
Affiliations
  • Tohoku University (JP)
  • National Institutes of Health (US)
Corresponding author
Maeda, Hiroshi
ORCID
Khatami, Mahin
Venue
Clinical and Translational Medicine
Publisher
Wiley
Published
2018-03
Volume
7
Issue
1
Pages
11-11
ISSN
2001-1326 (ISSN-L)
DOI
10.1186/s40169-018-0185-6
PMC
PMC5852245
OpenAlex
W2799710201
Cited by
491
References
146
Citations by year
2026: 29 · 2025: 61 · 2024: 63 · 2023: 63 · 2022: 94 · 2021: 67 · 2020: 71 · 2019: 37 · 2018: 6
FWCI
16.96
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical and Translational Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Pennsylvania
  • Ministry of Education, Culture, Sports, Science and Technology
  • National Institutes of Health
  • Japan Society for the Promotion of Science (17016076)
  • National Eye Institute (EY03984)
  • National Cancer Institute
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
solid tumors, targeted therapy, molecularly targeted agents, kinase inhibitors, growth factor receptor inhibitors, tumor heterogeneity, drug development, cancer vaccines, HPV vaccine, flu vaccine, cancer treatment costs, immunotherapy, cancer incidence

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