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Background of Molecular Oncology

Molecular oncology is an important medical branch of tumor research that has emerged in recent years. It aims to study cancer or tumor at the molecular scale and ultimately apply them to cancer treatment. Oncological studies on cell membrane proteins mainly focus on the immune recognition response of cancer cells and their use as targets for anticancer drug delivery.

Molecular Oncology Immunotherapy

Molecular oncology immunotherapy attempts to recruit the immune system to attack cancer by simultaneously overcoming the tumor's ability to evade the immune system and upregulating the strength of the immune system. The currently available cancer treatment is combining CAR-T with checkpoint inhibitors and cytokines. There are two commonly used membrane protein targets for checkpoint inhibitors that are designated as cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein (PD-1).

Fig.1 Structure Prediction of CTLA-4.Fig.1 Structure Prediction of rat CTLA-4.1

Application and Pathology of Oncology Cell Lines

Oncological research on cell membrane proteins has a huge impact on the field of cancer therapy and provides brand-new aspects to tumor studies. Many cancer cells can evade the damage from the immune system by overexpressing ligands that inhibit these checkpoints and suppress T cell attack, this mechanism and the molecules and proteins involved have been extensively studied via oncology cell lines. At present, oncological research on cell membrane proteins mainly focuses on enhancing the attack desire of immune cells or using specific antigens on the surface of cancer cells as drug delivery targets to kill cancer cells.

Published Data

Paper Title Liver cancer cell lines treated with doxorubicin under normoxia and hypoxia: cell viability and oncologic protein profile
Journal Cancers
Published 2019
Abstract Hepatocellular carcinoma (HCC) is usually treated with high concentrations of drugs and a hypoxic environment. The synergistic effect of the combined administration of targeted drugs and embolization in patients is extremely difficult to distinguish in the laboratory environment, making delays in the targeted research process. In order to separately evaluate the synergistic effect of drugs and hypoxic environment, the researchers exposed the liver cancer cell lines SNU449, HepG2, and Huh7 to targeted drug, hypoxia or hypoxia/targeted drug environment, and evaluated the healing effect produced by experiencing different incubation times under different conditions. In this experiment, cell viability, oxidative stress, and apoptosis were used as indicators of therapeutic response, and pharmacokinetic analysis under different conditions was performed. Hypoxic environmental limits reduced the viability of HepG2 and SNU499, and SNU449 showed the highest resistance to targeted drugs, while HepG2 had lower normalized protein expression than Huh7 and SNU449. These three common HCC cell lines responded distinctly to chemotherapy and hypoxia and were clearly reflected in distinct protein expression profiles.
Result In this study, researchers report that three established and commonly used liver cancer cell lines (HepG2, Huh7, and SNU449) respond distinctly to chemotherapy and hypoxia. This is also reflected in their oncogenic protein profiles and their responses to hypoxia and oxidative stress. The synergistic effect of hypoxia and doxorubicin (DOX) treatment was only observed in HepG2 cells, whereas Huh7 and SNU449 may have developed a mechanism to evade treatment and hypoxia, which are critical when studying chemotherapeutic agents.
Tumor cell adaptation to hypoxia is thought to be a major driver of selection for a more aggressive and therapy-resistant cancer phenotype. Experimental results highlight the need to account for inter- and intra-tumor heterogeneity and to include multiple cell lines in preclinical studies. The data further suggest that tumors respond differently to the combination of local chemotherapy and embolization, which is important for future treatment optimization. This treatment is usually a combination of local intrahepatic administration of one or more chemotherapeutic agents, combined with or subsequent occlusion of tumor-feeding vessels. The treatment serves two purposes: to obtain high local chemotherapeutic tumor concentrations and to create a hypoxic environment to induce synergistic cell death. However, the findings suggest that similar oncology interventions may not always be the best strategy. The results may support many clinical findings that the combination of vascular occlusion and chemotherapy treatment does not increase overall survival.

Fig.2 The effect of different treatments on cell viability.Fig. 2 The effect of different treatments on cell viability over time.2,3

References

  1. Image retrieved from Alphafold (Uniprot ID A0A096MJE4), used under CC BY 4.0, without any modification.
  2. Dubbelboer, Ilse R., et al. "Liver cancer cell lines treated with doxorubicin under normoxia and hypoxia: cell viability and oncologic protein profile." Cancers 11.7 (2019): 1024.
  3. Image retrieved from Figure 1 "The effect of different treatments on cell viability over time." Dubbelboer, et al. 2019, used under CC BY 4.0. The original image was modified by extracting and the title was changed to " The effect of different treatments on cell viability over time.".

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