mRNA expression, tumor heterogeneity, and response to therapy in patients with advanced renal cell carcinoma treated

Cristina Aguzzi1, Simona De Summa2, Javier Molina-Cerrillo3

  • 1School of Pharmacy, University of Camerino, Camerino, Macerata, Italy.

Abstract

Insights

Investigating 32 gene mRNA expression in advanced renal cell carcinoma (RCC) revealed potential links to immune therapy response. Tumor heterogeneity, particularly VEGFA deregulation, was observed between primary and metastatic sites.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunotherapy

Background:

  • Renal Cell Carcinoma (RCC) is a complex cancer with diverse characteristics and varied responses to immune-based treatments.
  • Understanding the molecular underpinnings of RCC is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the mRNA expression of 32 genes linked to RCC carcinogenesis.
  • To explore the potential role of these genes in patients receiving first-line immune-based combination therapies.
  • To assess tumor heterogeneity by comparing gene expression between primary and metastatic RCC sites.

Main Methods:

  • Retrospective analysis of 17 advanced RCC patients treated with first-line immune-based therapies.
  • Quantitative reverse transcription-polymerase chain reaction (RT-PCR) to analyze mRNA expression of 32 genes.
  • Comparison of mRNA expression levels between primary tumors and metastatic sites.

Main Results:

  • Higher mRNA expression of the analyzed genes correlated with better response to immune therapy.
  • Lower mRNA expression was associated with primary refractoriness to first-line therapy.
  • VEGFA was the only gene significantly deregulated when comparing primary and metastatic RCC samples, indicating tumor heterogeneity.

Conclusions:

  • Differences in mRNA expression exist between primary and metastatic RCC sites.
  • Gene expression patterns may be linked to treatment response in advanced RCC.
  • Further research is needed to validate these genes as prognostic or predictive biomarkers for RCC.

Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
660
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.1K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K