Biology Reference
In-Depth Information
7. Perform Patient Testing for Biomarkers as
Soon as Cancer Is Identified
This is predicated on the development of reliable,
clinically available testing methods as already noted in
bucket 5. Testing for biomarkers will help identify
patients who are most likely to respond to particular
DNA repair inhibitor treatments.
5
It will also enable
clinicians to start treatments earlier, which should yield
better outcomes.
capacity than men. Customizing regimens in this way
should still deliver effective tumor
killing
treatments while also decreasing the accumulation of
mutations in normal cells.
7
e
Consider the stage of cancer as well as the type of
cancer in selecting treatment, as both manifest
different levels of DNA repair abilities.
Similarly, take into account the degree and extent of
hypoxia, as hypoxia correlates with radioresistance.
27
Look for the unexpected, such as counterintuitive
approaches to rational combination. For example, two
emerging potential reasons for combining PARPi with
drugs are: the potential vasoactivity of PARPi can lead
to greater drug delivery
11
and PARPi can have
protective effects on quiescent normal tissues.
28
8. Restructure Clinical Trials
Currently, trials look for the right treatment for the
average patient
not
each
patient. Develop large,
prospectively designed clinical trials to assess the
impact and cost-effectiveness of pretreatment genotyp-
ing approaches for targeted patient therapy (see Chapter
12). Taking advantage of molecular characterization will
improve the chances of successful trials on a more tar-
geted patient population.
26
e
As researchers strive to accomplish the goals in each of
these nine buckets of activities, we move closer to truly
customized patient therapy and better patient outcomes
in the fight against cancer.
Acknowledgments
Financial support for this work was provided by the National Insti-
tutes of Health, National Cancer Institute CA121168, CA114571, and
CA121168S1 to M.R.K. Additional financial support was provided by
the Riley Children's Foundation and the Earl and Betty Herr Professor
in Pediatric Oncology Research to M.R.K. Also, thanks to Lana Chris-
tian of CreateWrite, Inc., for her writing and editing assistance. Addi-
tional thanks to Julie Driscol for her help expediting and proofing this
and other chapters of this topic.
9. Rethink Anticancer Regimens
Basing regimens on molecular patient profiles in
addition to “traditional” demographics (age, gender,
ethnicity, type of cancer, what stage it is in, etc.) will
increase the chances of eradicating the cancer. Such
profiles could have wide-ranging effects and could
spawn new treatment regimens. A few suggested appli-
cations follow:
References
Use DNA repair inhibitors as minimally toxic agents
in treating premalignant or early neoplastic lesions, as
tumor inactivation of DNA damage signaling and
DNA repair is often a relatively early event during
carcinogenesis.
5
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