Disease persists or recurs:
Why do disease treatments fail, in the treatment of AML et al if the
residual tumor cells are antigenically similar progeny of the originals?
Simply the effect of mutagenic chemotherapy? Or subclones of the blast
or progenitor population? Or do the blasts evolve and develop subsequent
resistance to any and all therapeutic agents? AML is the best suited
model for laboratory investigation as the disease mimics the accepted
cancer stem cell model.
Controversially the definition of cancer stem cells (CSC) is not yet
settled: is the CSC an initiating cell, a propagating cell, or a
stem-like cell?
Evolutionary changes in the body, dependent on both the external and
internal environment (chemo and immune-therapy), allow diseases to
escape natural controls i.e. the immune system, and provide shields to
further treatment. Sequencing of paired initial and relapse AML cells
reveal relapse is reflected in minor genetic subclones initially present
which survive chemotherapy. What are these cells?
Similarly, in lymphoma, tumor cells evolve to become refractory to
chemotherapy, loss of responsiveness to treatment with monoclonal
antibodies (mAbs) such as rituximab and that is a serious complication
during therapy of B-cell malignancies, but the mechanisms responsible
for it are not well understood.11
This is what one would expect from natural kinds such as ourselves; we
evolve to survive ambient cultures e.g. obesity and Type II diabetes may
be considered evolutionary alterations22 a shift from simpler
diets and activities.
The most important advance provided for in the concept of precision
medicine initiative will be a more specific way to define and thus to
understand disease, but it will not finally be therapeutically effective
since natural kinds will not easily succumb to alteration of the
interior milieu i. e. the treatment that will try to change this
interior state.3312 Natural kinds will adapt to interventions
as quickly as they can.
As precision medicine is aimed at understanding disease, we must be able
to take advantage of survival distributions; if every disease is unique,
there is no purchase for induction, nor path to generalize treatment If
each case of lung cancer will require different immunomodulating
drugs,1344 and the cost for one year exceeds $150,000, or CART
therapy with axicabtagene costing $373,000 for a single injection, how
shall equitable distribution be established in the non-insured
population?55 667714
“There is a grandeur in this view of life (and disease) with its
several powers, having been originally breathed into a few forms or into
one; and that whilst the planet has gone cycling on according to the
fixed law of gravity, from so simple a beginning endless forms most
beautiful and most wonderful have been, and are being,
evolved.”88 15
Declarations:
- Ethics approval and consent to participate not applicable
- Consent for publication: Not applicable
- Availability of data and material: not applicable
- Competing interests: none
- Funding: none
- Authors’ contributions: single author
- Acknowledgements: Maine Medical Center Library
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