321Recurrent and Drug-Resistant Ovarian Cancer
To identify the best treatment for recurrent ovarian cancer, researchers at Yale
School of Medicine (Harford, CT) are studying a technology called the Yale apop-
tosis assay in combination with another technology called the ChemoFX assay,
which could double the response rate to existing drugs. In patients with recurrent
ovarian cancer, it is often diffi cult to select an effective treatment because the tumor
develops resistance to many drugs. Currently, physicians select a drug and must
wait about six months to see whether it is effective on a particular patient. These two
new assays will take the guesswork out of cancer treatment. Yale apoptosis assay is
based on a biological principle that when a drug is effective, it will induce apoptosis
in the cancer cell. If the cancer cell is resistant to a drug, apoptosis does not occur.
The ChemoFX assay will determine whether a drug stops tumor growth. Used
together, both assays will distinguish drugs that can stop the growth of the tumor
and/or kill the tumor. This was not possible before. The technology will be studied
with various cancers, starting with ovarian cancer. Each assay will be evaluated
independently and then in combination in a multicenter clinical trial. The Yale
research team partnered with Helomics, which has licensed and markets the
ChemoFX assay. A study in 2009 at Duke University showed that >50 % of physi-
cians followed results of ChemoFx ® in management of ovarian cancer and the
results changed physician behavior. Use of ChemoFx ® results in cost savings of
$2,900–$8,100 per patient per round for primary or recurrent ovarian cancer cases
over a six-cycle treatment period.
The high incidence of recurrence attributable to multidrug resistance and the
multiple histologic phenotypes indicative of multipotency suggests a stem cell-like
etiology of ovarian cancer. Breast cancer-resistance protein 1-expressing verapamil-
sensitive side population cells were identifi ed in human ovarian cancer cell lines and
primary ascites cells from patients with ovarian cancer. In the future, individualized
therapy must incorporate analysis of the stem cell-like subpopulation of ovarian
cancer cells when designing therapeutic strategies for ovarian cancer patients.
High-grade serous cancer (HGSC), the most common subtype of ovarian cancer,
often becomes resistant to chemotherapy, leading to poor patient outcomes.
Intratumoral heterogeneity occurs in nearly all solid cancers, including ovarian can-
cer, contributing to the development of resistance mechanisms. Past studies have
identifi ed a handful of resistance-related mutations in ovarian cancer, but unidenti-
fi ed CNVs could contribute to this process as well. A study has examined the spatial
and temporal genomic variation in HGSC using high-resolution Affymetrix SNP
6.0 arrays (Cowin et al. 2012 ). Multiple metastatic lesions from individual patients
were analyzed along with 22 paired pretreatment and posttreatment samples. The
authors documented regions of differential DNA copy number between multiple
tumor biopsies that correlated with altered expression of genes involved in cell
polarity and adhesion. In the paired primary and relapse cohort, they observed a
greater degree of genomic change in tumors from patients that were initially sensi-
tive to chemotherapy and had longer progression-free interval compared with
tumors from patients that were resistant to primary chemotherapy. Notably, deletion
Personalized Management of Cancers of Various Organs