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Related Concept Videos

The Tumor Microenvironment02:17

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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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.
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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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Targeting Tumor Microenvironment in Liver Cancers: Rationale, Current Progress, and Future Perspective.

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Newer cancer treatments like immunotherapy and antiangiogenic agents offer hope for advanced liver cancer patients. Combining these strategies, alongside radiation and chemotherapy, may improve survival rates for hepatocellular carcinoma (HCC) and other liver cancers.

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Area of Science:

  • Hepatobiliary and Pancreatic Oncology
  • Translational Cancer Research

Background:

  • Surgical resection offers curative potential for liver cancers but is often not feasible due to unresectable disease at diagnosis or post-surgical progression.
  • Limited efficacy of existing local and systemic treatments for advanced hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and metastatic pancreatic ductal adenocarcinoma (PDAC) results in poor survival rates.

Purpose of the Study:

  • To review recent advancements in oncology offering renewed hope for patients with advanced liver cancers.
  • To highlight the potential of novel therapeutic strategies, including hypofractionated radiation, antiangiogenic agents, chemotherapy, and immunotherapy, in managing unresectable liver malignancies.
  • To emphasize the need for further research into combination therapies and early-stage interventions for improved patient outcomes.

Main Methods:

  • Review of current and emerging treatment modalities for advanced liver cancers.
  • Discussion of clinical trials and preclinical studies investigating novel therapeutic approaches.
  • Emphasis on a "bench to bedside and back" translational research strategy.

Main Results:

  • Hypofractionated radiation shows promise in unresectable HCC and is under investigation in a Phase III trial.
  • Antiangiogenic agents (sorafenib, lenvatinib, regorafenib, cabozantinib, ramucirumab) have significantly impacted advanced HCC management.
  • Immunotherapy (anti-PD-1/PD-L1, anti-CTLA4) demonstrates potential in both first- and second-line settings for advanced HCC.
  • Chemotherapy remains the standard of care for ICC and PDAC.

Conclusions:

  • Combination strategies involving novel agents hold promise for durable and profound responses in advanced HCC.
  • Further mechanistic preclinical studies and correlative clinical trial validation are crucial for optimizing combination therapies.
  • Translational research is key to developing effective targeted agents in combination and for earlier disease stages, aiming to improve survival for aggressive liver cancers.