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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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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.
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Targeted Cancer Therapies02:57

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Cancer Vaccines01:30

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Cancer treatment vaccines are a rapidly evolving field that offers a promising approach to immunotherapy. Unlike traditional vaccines that prevent diseases, cancer treatment vaccines are designed to treat existing cancers by stimulating the immune system to recognize and attack cancer cells.
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
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Current Advances and Future Directions for Sensitizing Gastric Cancer to Immune Checkpoint Inhibitors.

Wenke Li1, Menghui Xu1, Mo Cheng1

  • 1Gastric Cancer Center/Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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Summary

Novel combination therapies are being explored to improve outcomes for HER2-negative gastric cancer (GC) patients, addressing limited benefits from current immunotherapy and chemotherapy standards. Research focuses on overcoming resistance and personalizing treatment strategies for better survival.

Keywords:
PD‐1/PD‐L1 inhibitorsgastric cancerimmunotherapyimmunotherapy sensitization

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Area of Science:

  • Oncology
  • Immunotherapy
  • Cancer Research

Background:

  • Current immunotherapy plus chemotherapy for HER2-negative gastric cancer (GC) offers limited survival benefits (mPFS 6-8 months, mOS 15-18 months).
  • Outcomes are particularly poor for patients with a Combined Positive Score (CPS) < 1.
  • Tumor heterogeneity and resistance mechanisms present significant challenges, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To explore novel combination therapies for gastric cancer (GC).
  • To investigate strategies for overcoming immunotherapy resistance in GC.
  • To improve response rates and survival outcomes in GC patients.

Main Methods:

  • Investigating combination therapies including anti-VEGF with immune checkpoint inhibitors (ICIs).
  • Exploring radiotherapy combined with ICIs to modulate the tumor microenvironment.
  • Evaluating PD-1/PD-L1 inhibitors with targeted therapies (HER2, FGFR2, DKK1, PARP, LSD1, HDAC).
  • Examining novel approaches like hyperbaric oxygen, oncolytic viruses, metabolic modulators, and fecal microbiota transplantation.

Main Results:

  • Anti-VEGF and ICI combinations show synergistic effects, enhancing immune cell infiltration and reducing immunosuppression.
  • Radiotherapy with ICIs demonstrates potential in remodeling the tumor microenvironment and inducing immunogenic cell death.
  • Various targeted therapies and novel approaches are under investigation to enhance immune responses.

Conclusions:

  • Multimodal strategies offer a promising direction for personalized, mechanism-driven immunotherapy sensitization in GC.
  • These approaches aim to overcome immune resistance, reshape the tumor microenvironment, and restore immune responsiveness.
  • Future research should focus on optimizing combinations, understanding resistance, and identifying biomarkers using multi-omics and AI for individualized immunotherapy.