Ending Cancer

I get a creeping sense of subcutaneous unease that something is not quite right. There is fundamental misunderstanding about the role of genes in the healthy development of eggs to embryos and adults. Unfortunately, this abuse of the gene-centered view of life extends to multi-cellular diseases such as cancer. This view is doing real harm causing needless future suffering and death. Why? Because we are not attacking cancer at its core. I propose that to really cure cancer that we need a fundamental paradigm shift in how we understand, diagnose and treat cancer. On my view, cancer is not primarily caused by mutations in genes. The underlying drivers of cancers are networks that control the actions and dynamics of cells. I think a revolutionary rethinking needs to happen in our view of cancer. The problem is that scientists always try to understand a new theory or paradigm in terms of the concepts of the old paradigm. They then fail to understand the theory, because the concepts of the new theory cannot be expressed in terms of the old one.

Romanian Journal of Oncology and Hematology, 2013

TURKISH JOURNAL OF BIOLOGY, 2014

Cancer is probably the number one research area among all human endeavors, receiving the largest portion of science funding in most countries. This is because cancer remains one of the oldest conundrums among all human maladies. Although we now have a greater understanding of the biological and molecular basis of cancer, its diagnosis and therapy still pose great challenges. In this review, our aim is not to establish a comprehensive understanding of cancer, which is essentially impossible, but to outline, in a more provocative way, why cancer research in the pursuit of a cure did not live up to its promise, as the death rate from cancer has not changed much after almost half a century. In addition, we discuss some future perspectives to give some insight into cancer research and debunk the old view that pouring money into cancer research is the only way to overcome this dreadful disease.

Trends in molecular medicine, 2012

The theoretical framework for the field of cancer research is based on two main principles. The first is that cancer advances in a stepwise manner, with each alteration driving cells further toward a malignant state. Second, to cure cancer we must target only cancer-specific properties. Here, we analyze the birth and propagation of the cancer research paradigm. We believe the current paradigm is immersed in crisis and that the field would benefit from integrating theories within and outside the normal modes of research to compile a new framework, with the hope of faster progress and significantly fewer cancer-related deaths.

Biochemical Pharmacology, 2009

Current estimates from the American Cancer Society and from the International Union Against Cancer indicate that 12 million cases of cancer were diagnosed last year, with 7 million deaths worldwide; these numbers are expected to double by 2030 (27 million cases with 17 million deaths). Despite tremendous technological developments in all areas, and President Richard Nixon's initiative in the 1974 "War against Cancer", the US cancer incidence is the highest in the world and the cancer death rate has not significantly changed in the last 50 years (193.9 per 100,000 in 1950 vs 193.4 per 100,000 in 2002). Extensive research during the same time, however, has revealed that cancer is a preventable disease that requires major changes in life style; with one third of all cancers assigned to Tobacco, one third to diet, and remaining one third to the environment. Approximately 20 billion dollars are spent annually to find a cure for cancer. We propose that our inability to find a cure to cancer lies in the models used. Whether cell culture or animal studies, no model has yet been found that can reproduce the pathogenesis of the disease in the laboratory. Mono-targeted therapies, till know in most cases, have done a little to make a difference in cancer treatment. Similarly, molecular signatures/predictors of the diagnosis of the disease and response are also lacking. This review discusses the pros and cons of current cancer models based on cancer genetics, cell culture, animal models, cancer biomarkers/signature, cancer stem cells, cancer cell signaling, targeted therapies, therapeutic targets, clinical trials, cancer prevention, personalized medicine, and off-label uses to find a cure for cancer and demonstrates an urgent need for "out of the box" approaches.

Molecular Cancer Research, 2023

Most definitions of cancer broadly conform to the current National Cancer Institute definition: "Cancer is a disease in which some of the body's cells grow uncontrollably and spread to other parts of the body". These definitions tend to describe what cancer "looks like" or "does" but do not describe what cancer "is" or "has become." While reflecting past insights, current definitions have not kept pace with the understanding that the cancer cell is itself transformed and evolving. We propose a revised definition of cancer: Cancer is a disease of uncontrolled proliferation by transformed cells subject to evolution by natural selection. We believe this definition captures the essence of the majority of previous and current definitions. To the simplest definition of cancer as a disease of uncontrolled proliferation of cells, our definition adds in the adjective "transformed" to capture the many tumorigenic processes that cancer cells adopt to metastasize. To the concept of uncontrolled proliferation of transformed cells, our proposed definition then adds "subject to evolution by natural selection." The subject to evolution by natural selection modernizes the definition to include the genetic and epigenetic changes that accumulate within a population of cancer cells that lead to the lethal phenotype.

Cancer Studies and Molecular Medicine - Open Journal, 2020

E ven though cancer researchers nowadays are trying to develop many key cellular pathways susceptible to be tackled by therapeutic approaches, we are far from being able to consider some cancers as curable diseases in general terms. From a pharmacodynamic point of view, the main potential molecular targets involved are driver oncogenes, tumor suppressor genes, growth factors and their receptors, transcription factors, tyrosine kinases, and cell adhesion molecules. If we consider possible targets at higher organization levels, we can intervene in aspects such as chromatin organization, tumor microenvironment, angiogenesis, apoptosis, senescence, mitochondria metabolism, and immune pathways.

BMC Cancer, 2014

Since the "War on Cancer" was declared in 1971, the United States alone has expended some $300 billion on research, with a heavy focus on the role of genomics in anticancer therapy. Voluminous data have been collected and analyzed. However, in hindsight, any achievements made have not been realized in clinical practice in terms of overall survival or quality of life extended. This might be justified because cancer is not one disease but a conglomeration of multiple diseases, with widespread heterogeneity even within a single tumor type. Only a few types of cancer have been described that are associated with one major signaling pathway. This

International journal of oncology, 1999

Over the past few decades, there has been a tremendous increase in cancer biology data and treatment. Cancer research has opened exciting new areas of cellular and molecular biology. Month by month, new genes which regulate the carcinogenesis process are being discovered. The result is an incredible knowledge of cancer: what makes a cancer cell a cancer cell, what cancer cells need to develop, and how cancer cells behave, interact, overgrow and die. In parallel, gene manipulation within cells lets us foresee future possibilities of new cancer treatments. On the other hand, this combination of increased knowledge and powerful new techniques has provided no effective cancer therapy. As it has been quoted during the <Update and Intensive Review of Internal Medicine> meeting held in New York, August 1999: <. The success in treating Hodgkin's disease means that patients now live enough to develop complications related to the treatment>. Thus, after dedicated decades of ex...

Journal of Biosciences, 2014

Despite intense research efforts that have provided enormous insight, cancer continues to be a poorly understood disease. There has been much debate over whether the cancerous state can be said to originate in a single cell or whether it is a reflection of aberrant behaviour on the part of a 'society of cells'. This article presents, in the form of a debate conducted among the authors, three views of how the problem might be addressed. We do not claim that the views exhaust all possibilities. These views are (a) the tissue organization field theory (TOFT) that is based on a breakdown of tissue organization involving many cells from different embryological layers, (b) the cancer stem cell (CSC) hypothesis that focuses on genetic and epigenetic changes that take place within single cells, and (c) the proposition that rewiring of the cell's protein interaction networks mediated by intrinsically disordered proteins (IDPs) drives the tumorigenic process. The views are based on different philosophical approaches. In detail, they differ on some points and agree on others. It is left to the reader to decide whether one approach to understanding cancer appears more promising than the other.