Oncotarget: Hemoglobin increases the effectiveness of chemotherapy in lung cancer

Oncotarget recently published "Polymerized human hemoglobin increases the effectiveness of cisplatin-based chemotherapy in non-small cell lung cancer" which reported that unfortunately, a significant portion of NSCLC patients relapse due to cisplatin chemoresistance.

Administration of hemoglobin-based oxygen carriers is a promising strategy to alleviate hypoxia in the tumor, which may make cisplatin more effective.

The R-state PolyHb administered in this study is unable to deliver O2 unless under severe hypoxia which significantly limits its oxygenation potential.

In vitro sensitivity studies indicate that the administration of PolyHb increases the effectiveness of cisplatin under hypoxic conditions.

Additional animal studies revealed that co-administration of PolyHb with cisplatin attenuated tumor growth without alleviating hypoxia.

Additional animal studies revealed that co-administration of PolyHb with cisplatin attenuated tumor growth without alleviating hypoxia

Dr. Pedro Cabrales from The Department of Bioengineering at The University of California San Diego said, "Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer death and constitutes ~80 to 85% of all types of lung cancers."

Furthermore, the expression of HIF-1α is associated with the reduction of ROS in cancer cells, which promotes cancer cell survival.

In an attempt to reverse the tumor's hypoxic microenvironment, several studies have supplemented cisplatin treatment with hemoglobin-based oxygen carriers.

The above studies have been capable of effectively increasing the sensitivity of cancerous cells to cisplatin, both in vitro and in vivo, via supplementation of HBOCs, and they attribute this gained efficacy to increased O2 delivery.

However, the concentrations of HBOC used in previous studies were insufficient to provide a significant increase in tumor O2 delivery.

Figure 5: (A) Expression of HIF-1α and HIF-2α measured by Western blot analysis in the in-vivo A549 tumor. (B) Average intensity of the HIF-1α and HIF-2α bands for each experimental group, normalized to the vehicle control.

Hence, this study explores both mechanisms, i. e., the increase in oxygenation of the tumor and the catalyzed formation of ROS by the HBOC, in in vitro and in vivo studies using low molecular weight polymerized human Hb in the relaxed quaternary state.

The Cabrales Research Team concluded in their Oncotarget Research paper that this study serves as preliminary evidence of PolyHb's ability to increase the sensitivity to cisplatin in NSCLC.

The evidence presented in this study suggests that decreased hypoxia due to facilitated O2 delivery combined with endogenous O2 delivery in the animal might have a small effect on cisplatin sensitization.

Future studies should aim at utilizing in vivo approaches for both ROS detection and intravascular oxygenation in the implanted tumors, as an approach for determining the effects of PolyHb in these two essential processes.

Additionally, these studies should consider incorporating superoxide dismutase and catalase to evaluate the exact modes of ROS generation that influence the chemosensitization mechanism as a function of environmental O2 tension.

Future studies should also explore how the administration of PolyHb solutions modulates prolyl hydroxylase, gene expression, and protein expression after extended doses.

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DOI - https://doi.org/10.18632/oncotarget.27776

Full text - https://www.oncotarget.com/article/27776/text/

Correspondence to - Pedro Cabrales - pcabrales@ucsd.edu

Keywords - chemotherapy, cisplatin, polymerized hemoglobin, non-small cell lung cancer, hypoxia

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