In the abstract of ‘Hallmarks of Cancer: The Next Generation’ (4 March, 2011), the authors Douglas Hanahan and Robert A. Weinberg summarized the latest research findings as it pertains to the development of human cancers:
“The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list—reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the “tumor microenvironment.” Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.”
These hallmarks and characteristics of the “tumour environment” were adeptly summarized in their graphical representations which are reproduced below:
Figure 1. The Hallmarks of Cancer
This illustration encompasses the six hallmark capabilities originally proposed in our 2000 perspective. The past decade has witnessed remarkable progress toward understanding the mechanistic underpinnings of each hallmark.
Figure 2. Intracellular Signaling Networks Regulate the Operations of the Cancer Cell
An elaborate integrated circuit operates within normal cells and is reprogrammed to regulate hallmark capabilities within cancer cells. Separate subcircuits, depicted here in differently colored fields, are specialized to orchestrate the various capabilities. At one level, this depiction is simplistic, as there is considerable crosstalk between such subcircuits. In addition, because each cancer cell is exposed to a complex mixture of signals from its microenvironment, each of these subcircuits is connected with signals originating from other cells in the tumor microenvironment, as outlined in Figure 5.
Figure 3. Emerging Hallmarks and Enabling Characteristics
An increasing body of research suggests that two additional hallmarks of cancer are involved in the pathogenesis of some and perhaps all cancers. One involves the capability to modify, or reprogram, cellular metabolism in order to most effectively support neoplastic proliferation. The second allows cancer cells to evade immunological destruction, in particular by T and B lymphocytes, macrophages, and natural killer cells. Because neither capability is yet generalized and fully validated, they are labeled as emerging hallmarks. Additionally, two consequential characteristics of neoplasia facilitate acquisition of both core and emerging hallmarks. Genomic instability and thus mutability endow cancer cells with genetic alterations that drive tumor progression. Inflammation by innate immune cells designed to fight infections and heal wounds can instead result in their inadvertent support of multiple hallmark capabilities, thereby manifesting the now widely appreciated tumor-promoting consequences of inflammatory responses.
Figure 4. The Cells of the Tumor Microenvironment
(Upper) An assemblage of distinct cell types constitutes most solid tumors. Both the parenchyma and stroma of tumors contain distinct cell types and subtypes that collectively enable tumor growth and progression. Notably, the immune inflammatory cells present in tumors can include both tumor-promoting as well as tumor-killing subclasses.
(Lower) The distinctive microenvironments of tumors. The multiple stromal cell types create a succession of tumor microenvironments that change as tumors invade normal tissue and thereafter seed and colonize distant tissues. The abundance, histologic organization, and phenotypic characteristics of the stromal cell types, as well as of the extracellular matrix (hatched background), evolve during progression, thereby enabling primary, invasive, and then metastatic growth. The surrounding normal cells of the primary and metastatic sites, shown only schematically, likely also affect the character of the various neoplastic microenvironments. (Not shown are the premalignant stages in tumorigenesis, which also have distinctive microenvironments that are created by the abundance and characteristics of the assembled cells.)
Figure 5. Signaling Interactions in the Tumor Microenvironment during Malignant Progression
(Upper) The assembly and collective contributions of the assorted cell types constituting the tumor microenvironment are orchestrated and maintained by reciprocal heterotypic signaling interactions, of which only a few are illustrated.
(Lower) The intracellular signaling depicted in the upper panel within the tumor microenvironment is not static but instead changes during tumor progression as a result of reciprocal signaling interactions between cancer cells of the parenchyma and stromal cells that convey the increasingly aggressive phenotypes that underlie growth, invasion, and metastatic dissemination. Importantly, the predisposition to spawn metastatic lesions can begin early, being influenced by the differentiation program of the normal cell-of-origin or by initiating oncogenic lesions. Certain organ sites (sometimes referred to as “fertile soil” or “metastatic niches”) can be especially permissive for metastatic seeding and colonization by certain types of cancer cells, as a consequence of local properties that are either intrinsic to the normal tissue or induced at a distance by systemic actions of primary tumors. Cancer stem cells may be variably involved in some or all of the different stages of primary tumorigenesis and metastasis.
Figure 6. Therapeutic Targeting of the Hallmarks of Cancer
Drugs that interfere with each of the acquired capabilities necessary for tumor growth and progression have been developed and are in clinical trials or in some cases approved for clinical use in treating certain forms of human cancer. Additionally, the investigational drugs are being developed to target each of the enabling characteristics and emerging hallmarks depicted in Figure 3, which also hold promise as cancer therapeutics. The drugs listed are but illustrative examples; there is a deep pipeline of candidate drugs with different molecular targets and modes of action in development for most of these hallmarks.
Although the cellular aspect of cancer is very interesting and carries much import as it pertains to a better understanding of the underlying mechanism of its development and its treatment, I submit this framework also best exposes a social cancer, by helping to identify the parallel social hallmarks, enabling social characteristics and the social “tumour microenvironment” that undergirds its initiation, continuous development, and treatment, if so recognized and diagnosed. As you may have guessed, much of the motivation here is to throw some light and expose the social cancer in our midst, which truth be told is the secret to the ill-health of all nations.
So where do we start. A clue can be found in this article, ‘The Great American Bubble Machine‘, where the social cancer stem cells are identified, as they “may be variably involved in some or all of the different stages of primary tumorigenesis and metastasis”, thus providing the social parallel to the cancer stem cells identified in Figure 5 above. This corroborates Prof McMurtry’s claim, in print more than once, that the root cause of all causes of our globalised ill-health is the cancerous stage of capitalism that is “stem-celled in Wall Street”. This is also spelled out more fully by Michael Hudson in his book, ‘Killing the Host: How Financial Parasites and Debt Bondage Destroy the Global Economy‘ and by Greece’s former financial minister and economist Yanis Varoufakis in his book, ‘The Global Minotaur: America, the True Origins of the Financial Crisis and the Future of the World Economy‘.
We can also look further to identify in parallel fashion the hallmarks of this social cancer, and identify the social capabilities acquired in their development and metastases from Wall Sreet via the transnational corporations to Main Street.
We will now use the template of hallmarks in Figure 6 to further expose in point form the social correlates of the cancer cellular hallmarks.
- Sustaining proliferative signalling –> repealing of Glass-Steagel Act
- Evading growth suppression – – > NAFTA, WTO, and proposed investor-protection “trade” agreements – TPP, TTPA, and TISA
- Avoiding immune destruction –> removal of parliamentary oversight of investor-protection “trade” agreements, as these deals are done behind closed doors and are unreadable by the people’s representatives, given their volume and the legal jargon involved
- Enabling replicative immortality – -> as attempted by quantitative easing strategies in many parts of the world, and the expectation of unlimited exponential growth despite our living on a life-resources finite planet
- Tumour-promoting inflammation –> capture of government and politicians and other guardians of civic society that pass laws to open up avenues for their spread, such as via tax incentives and via tax havens
- Activating invasion and metastases – -> please read John Perkins’ updated book ‘The New Confessions of an Economic Hitman“
- Inducing angiogenesis – via legally binding “trade” diktats that open new avenues and pipelines of trade and transactions
- Genome instability and mutation – please see the IMF working paper, ‘Systemic Banking Crisis: A New Database.’
- Resisting cell death –> with previous bank bail-outs and the future expected bank bail-ins at the next financial crisis
- Deregulating cellular energetics –> funneling money capital from all of the above into transnational corporations via pump and dump options in the Stock Market, and via stock buy backs, transfer pricing, etc, rather than the productive life-energies of Main Street enabling unused resources meeting unmet needs.
(Several books can be written on each of these social cancerous hallmarks, which is beyond the aim and scope of this article. Hopefully by beginning to expose the unrecognised hallmarks of this cancerous development scheme, concrete steps can now be taken to confirm the diagnosis and a treatment plan initiated. Please note, that by increasing the depth and breath of focus, as more mechanisms come to light, the exposition shown above can be enlarged, further helping to expand the mechanisms involved in the evolution of the cancerous stages of our capitalism.)
As a medical practitioner, this exposure is very troubling to say the least, especially when we attempt to identify the stage of this social cancer, given that the prognosis gets worse and the prospects of remission and cure become more and more remote the later the stage.
As shown at http://www.cancer.gov/about-cancer/diagnosis-staging/staging/staging-fact-sheet, there are two clinical staging systems:
“The TNM system is one of the most widely used cancer staging systems. This system has been accepted by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC). Most medical facilities use the TNM system as their main method for cancer reporting.
The TNM system is based on the size and/or extent (reach) of the primary tumor (T), the amount of spread to nearby lymph nodes (N), and the presence of metastasis (M) or secondary tumors formed by the spread of cancer cells to other parts of the body. A number is added to each letter to indicate the size and/or extent of the primary tumor and the degree of cancer spread.
Primary Tumor (T)
TX: Primary tumor cannot be evaluated
T0: No evidence of primary tumor
Tis: Carcinoma in situ (CIS; abnormal cells are present but have not spread to neighboring tissue; although not cancer, CIS may become cancer and is sometimes called preinvasive cancer)
T1, T2, T3, T4: Size and/or extent of the primary tumor
Regional Lymph Nodes (N)
NX: Regional lymph nodes cannot be evaluated
N0: No regional lymph node involvement
N1, N2, N3: Degree of regional lymph node involvement (number and location of lymph nodes)
Distant Metastasis (M)
MX: Distant metastasis cannot be evaluated
M0: No distant metastasis
M1: Distant metastasis is present
For example, breast cancer classified as T3 N2 M0 refers to a large tumor that has spread outside the breast to nearby lymph nodes but not to other parts of the body. Prostate cancer T2 N0 M0 means that the tumor is located only in the prostate and has not spread to the lymph nodes or any other part of the body.
For many cancers, TNM combinations correspond to one of five stages. Criteria for stages differ for different types of cancer. For example, bladder cancer T3 N0 M0 is stage III, whereas colon cancer T3 N0 M0 is stage II.
Stage
Definition
Stage 0
Carcinoma in situ
Stage I, Stage II, and Stage III
Higher numbers indicate more extensive disease: Larger tumor size and/or spread of the cancer beyond the organ in which it first developed to nearby lymph nodes and/or tissues or organs adjacent to the location of the primary tumor
Stage IV
The cancer has spread to distant tissues or organs
Undeniably, we are at Stage IV of this social cancer given that it has metastasized to every aspect of the social landscape.
The question we all now have to ask is are we at the terminal stage of the social life-host organisation and is the only treatment now palliative? If we are not at this stage yet and we need to be hopeful, how do we induce this social cancer to go into remission or even effect a cure?
Again we turn to the cellular cancer, as there have recently been a breakthrough in harnessing our immune system to detect and target for destruction tumour cells. (Please see Cancer tumour genetics reveal possible treatment revolution.)
The answer lies again on the exposure of our social immune system and its stage of development, to which we will delve in more detail in the next blog article.
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