study was conducted at the Abramson Cancer Center, University of Pennsylvania,
Philadelphia, PA, USA.
published in Cancer Discovery
, was led by Dr. Irfan A. Asangani, PhD, who is an
Assistant Professor of Cancer Biology in the Perelman School of Medicine at the
University of Pennsylvania, Philadelphia, PA, USA.
What is the Link between CDK7 and Prostate
Cyclin-dependent kinase 7 (CDK7), also known as cell division protein kinase 7,
is a serine/threonine kinase that is specific to humans and is encoded by the CDK7
gene. CDK7 belongs to a class of
intracellular proteins, collectively known as cyclin-dependent kinases
(CDK) that are activated by binding to a cyclin, which mediates the progression
through the cell cycle.
In the present
study, it was found that CDK7 acts as a molecular "on/off" switch that
regulates the expression of MED1 (mediator
of RNA polymerase II transcription subunit 1), a human-specific protein encoded
by the MED1
gene, which functions as
a nuclear receptor co-activator. CDK7 and MED1 works in conjunction with the
androgen receptor (AR) to drive the growth and progression of prostate cancer
The research team found that turning "off" the molecular switch by
blocking CDK7 with a specific drug molecule, resulted in the death of the
prostate cancer cells, thereby halting cancer progression in a mouse model of
What are the Drawbacks of Current Therapies
for Prostate Cancer?
The currently used
standard treatment for prostate cancer
involves androgen deprivation
. However, the major
drawback of this treatment modality is that many patients become resistant to
the therapy, as a result of which cancer growth continues unabated and eventually
undergoes metastasis. This is referred to as metastatic castration-resistant
prostate cancer (CRPC).
drugs are currently available for treating CRPC, but these have shown very
little benefit for the long-term
survival of prostate cancer patients
What is the Mechanism of Action of the New
The new therapeutic
strategy takes into account that the androgen receptor
(AR) is the major driver of cancer growth in CRPC
. Therefore, taking
away its function would have a major negative impact on the survival of cancer
"We know that AR does
not work alone; that it needs MED1 as its partner,"
says Asangani. "Our study found a way to turn off MED1,
leaving AR without its co-pilot,
which means the cancer cannot grow and the cells eventually die."
team used a specific drug molecule that switched "off" CDK7 activity,
resulting in the death
of the CRPC cells in both laboratory settings and in animal models.
Importantly, there were hardly any off-target effects of this strategy,
indicating that only the cancer cells were killed, leaving the healthy host
CDK7 inhibitors are
currently undergoing evaluation in Phase I clinical trials for other types of
cancer, such as leukemia
cancer, glioblastoma (a type of brain cancer), and breast cancer
. Importantly, the present study showed
that this approach could also be effective in case of prostate cancer, which
warrants further testing in human clinical trials.
Asangani concludes: "Our
theory is that these cancer cells are addicted to MED1 and AR but other cells
are not, so we're essentially cutting them off from their addiction."