Exception is immunotherapy, but even this doesn’t widely apply and can have harsh side effects bc such efficient killing
Focus must be on prevention and early detection, eliminating the first cancer cell
Chapter 1
Slash/cut/burn protocol of tx (surgery, chemo, radiation) is often extremely painful— how often is no tx or palliative care offered as an option?
Limitations of cellular and mice models of cancer
“If you’re a mice and you have cancer, we can take good care of you.”
Major differences btw mice and humans = much faster life cycle, metabolism of mice vs humans; difference in environment of evolution
Immune systems evolved to combat different types of pathogens → different compositions
Therapies that work both in vitro and in clinical settings are usually general cytotoxic agents (not specific to a gene or physiological process)
Even PDXs not particularly effective
Need for fundamental shift in approach to treating cancer- interdisciplinary, multi-faceted
Shift from studying animals → humans
Shift from chasing the last cancer cell → detecting the first
Currently, too much dependence on leaders in the field, grant funding, mentors
Can’t get grant $$ without an animal model
Doctors need to spend more time with patients, understand the language of their illness, not just reaching for the first drug possible
Hippocratic Oath — “there is art to medicine as well as science”
Chapter 2
Critical states and self-organization of sand— grain that causes a sand pile to collapse is no different than the rest → metaphor applies to cancer initiation as well
Suggests need to examine overall health (the soil) in addition to the first cell (the seed)
Accumulation of DNA mutations, exposure to internal and external cancer-causing agents (including pathogens like viruses, mutations to proto-oncogenes or tumor suppressor genes)
Peto’s Paradox → mechanisms in large-bodied animals to prevent cancer
Value of comparative animals studies
Cancer is a multi-organ disease almost immediately after it begins, even when confined to single site
“The mist of aging” leading to cancer in the elderly — accumulation of mutations, decrease in functioning of immune system (like all biological systems with age), increase in number of senescent cells, tissue loss with age → spatial reorganization of cells
Chapter 3
Precision medicine? Due to such heterogenous response to drugs
Identity molecular features of “unicorn” exceptional responders
Requires saving biosamples of biopsies of tumors, microenvironment— not being done currently
However: few cases of one gene driving malignancy; such mutations often don’t have matched drugs; even if there is, response rate remains low; and response only may mean an added 6 months vs other therapies
Clonal composition of cancer → no person has one cancer; why one therapy rarely works forever
Chapter 4
Research funding system is screwed up
Chapter 6
Responsibility of oncologists to give patients efficacy, to offer all (applicable) treatment options
Currently often lack of trust btw doctor and patient → patients and their families Google all sorts of things
Hope can be as harmful a disease as cancer
Shift focus from tx targeting single genes to big data, omics, detecting DNA/RNA/proteins from the first cancer cells