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Cell Death Pathways in Targeted Therapy for Renal Cell Carcinoma

By: Melissa E. Fryman, MS
Posted: Thursday, December 19, 2019

Treatment of renal cell carcinomas is often characterized by off-target side effects and drug resistance that arise during chemotherapy. Due to the myriad barriers against traditional drug treatment, patients have limited options, such as resection for early-stage cancers and targeted therapies for metastatic disease. In a review article published in Cancer Cell International, Wenqi Wu, MD, of The First Affiliated Hospital of Guangzhou Medical University in Guangdong, China, and colleagues discuss current targeted therapies for renal cell carcinoma, as well as promising strategies that incorporate T-cell–induced cell death.

The authors focused on the main approved treatments for renal cell carcinoma, such as gemcitabine and doxorubicin, interleukin-2, interferon-a, and bevacizumab, as well as drugs targeting the VEGF tyrosine kinase inhibitor, mTOR, and programmed cell death pathways. The authors cited the limited predictive clinical benefit of these drugs, in part due to a lack of specific biomarkers, and intratumor heterogeneity, often seen in clear cell renal cell carcinoma.

Dr. Wu and colleagues also discussed the current compounds available to target the apoptosis protein molecules associated with renal cell carcinoma, such as members of the Bcl-2 family, inhibiting apoptosis inhibitors, caspase3, PD-1/PD-L1, NF kappa B, and CTLA-4. They further explored other types of cell death, such as necroptosis, ferroptosis, and autophagic cell death, as well as their potential role in the progression of this type of kidney cancer.

Lastly, the authors featured evidence in support of combination targeted therapies. Of note, they highlighted the use of tyrosine kinase inhibitors with immune checkpoint inhibitors or a combination of immune checkpoint inhibitors to activate T-cell–induced cell death as promising avenues worthy of study, as well as these treatments in combination with other cell death–related signaling pathways.

Disclosure: The study authors reported no conflicts of interest.



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