Team from Korea
University Medicine Explores Ways to Overcome Cisplatin Resistance and Alleviate Pain in Cancer
Treatment
for Major
Depressive Disorder
Researchers elucidate the biological
pathways leading to cisplatin resistance in patients with cervical cancer
Cisplatin is a widely used chemotherapy drug for various types of cancers. However, frequent usage can
lead to the development of drug resistance and neuropathic pain, eventually resulting in treatment
failure. In a new study, researchers from South Korea investigated the underlying pathways contributing
to this resistance and identified potential therapeutic targets that can be modulated to overcome this.
By understanding and targeting these mechanisms, effective treatment strategies can be developed and
implemented.
Image title: Pathway of cisplatin resistance in
cervical cancer
Image caption: The study reveals that the transcription factor NANOG activates the transient
receptor potential vanilloid 1 (TRPV1)—causing neuropathic pain. TRPV1 further stimulates the
EGFR signaling pathway, thus leading to cisplatin resistance
Image credit: Tae Woo Kim from Korea University Medicine
License type: Original Content
Usage restrictions: Cannot be reused without permission
Cisplatin is a potent chemotherapeutic agent used to treat various cancers, including cervical cancer.
But the continued use of cisplatin can lead to the development of cisplatin resistance and other side
effects, like chemotherapy-induced neuropathic pain. Overcoming these issues is a critical concern in
cervical cancer treatment.
Now, in a new study, Prof. Tae Woo Kim from Korea University Medicine and his team have explored the
pathways leading to cisplatin resistance. Their study was published online on 10 May 2023 in
Nature
Communications.
The team analyzed the transcriptome of patients with cervical cancer who had undergone surgery and found
that elevated epidermal growth factor receptor (EGFR) activity scores were associated with poor overall
survival in cisplatin-treated patients. "EGFR is a protein involved in cell signaling and its
dysregulation leads to uncontrolled cell growth and tumor formation. We conducted experiments on EGFR
signaling using cervical cancer cell lines and observed that the cisplatin-resistant cell line exhibited
hyperactivated EGFR signaling compared to the cisplatin-susceptible cells. This led us to conclude that
hyperactive EGFR triggers resistance mechanisms, leading to decreased drug effectiveness in tumor
cells," explains Prof. Kim.
The team further identified NANOG, a transcription factor associated with resistance, metastasis, and
stem cell-like properties in cancer cells, to be involved in the regulation of the EGFR pathway. They
discovered that NANOG activates the transient receptor potential vanilloid 1 (TRPV1), which is
responsible for causing neuropathic pain. TRPV1 further promotes a process called secretory autophagy,
which leads epidermal growth factor (EGF) secretion. EGF, in turn, activates the EGFR signaling pathway,
contributing to cisplatin resistance. “Most noteworthily, in our study, inhibiting TRPV1 using AMG9810,
a potential pain-relieving agent, rendered the resistant tumors vulnerable to cisplatin,” says Prof.
Kim.
This study serves as valuable proof-of-concept for TRPV1 as a therapeutic target to combat cisplatin
resistance and neuropathic pain, thereby improving the outlook for patients with cervical
cancer.
ReferenceTitle of original paper:TRPV1 inhibition overcomes cisplatin resistance by blocking
autophagy-mediated hyperactivation of EGFR signaling pathway
Journal:Nature Communications
DOI:
https://doi.org/10.1038/s41467-023-38318-7
About the Korea University Medicine
Korea University (KU), located in Seoul, South Korea, is a leading university established in 1905,
renowned for its academic excellence and contributions to higher education. Within KU, Korea University
Medicine (KU Medicine) is a top-ranked medical institution, comprising campuses like Anam Hospital, Guro
Hospital, Ansan Hospital, Cheongdam Goyeong Campus, and Jeongneung Mediscience Park. KU Medicine also
has educational institutions affiliated to it, including the College of Medicine, Graduate School of
Public Health, and Graduate School of Clinical Dentistry, driving remarkable advancements in medical
treatment, education, research, and social contributions.
Website:
https://www.kumc.or.kr/en/index.do
About the author
Prof. Tae Woo Kim received his Ph.D. from Korea University, Seoul, Republic of Korea, in 2000 and then
trained at Johns Hopkins University, School of Medicine, Baltimore, MD, USA during his postdoctoral
course. Then he joined Graduate School of Medicine, Korea University, Seoul, Republic of Korea in 2005,
where he is currently a professor. His laboratory has focused on the elucidation of the mechanism of
tumor immune escape and the understanding of malignant evolution of tumor cells after cancer treatment.
Based on those, he has tried to develop a novel modality for the control of immune-refractory tumors.