David Grainger, Distinguished Professor in the Department of Biomedical Engineering, believes bacteria living inside and around tumors may play a larger role in cancer therapies than previously recognized.
In a new analysis published in the journal Cancer Biology & Medicine, Grainger and co-authors from China’s Tianjin Medical University and Nankai University examine whether bacteria frequently found within certain aggressive solid tumors could help explain why some cancers remain difficult to treat despite decades of advances in cancer therapy. Their work focuses on aggressive solid cancers that often have poor treatment outcomes, pointing to colorectal and pancreatic cancers as examples of tumors that frequently resist treatment.
Grainger’s interest in the topic grew from his long-standing research in drug delivery and biomaterials, especially nanomaterials. For decades, scientists have worked to improve cancer treatments by developing nanoparticles to improve drug delivery to tumors. Their clinical promise, however, has not yet paid off as anticipated.
“Nanotechnology is frequently advocated to improve drug delivery and efficacy against solid tumors. But to date, despite 50 or so new drugs approved using nanotechnology, clinical data generally show no significant improvements in their anti-tumor therapeutic efficacy,” says Grainger. “So far, they’ve shown some reductions in the drugs’ toxic side effects on patients, but they are not increasing their lifespans. This has been disappointing to all stakeholders.”
At the same time, increasing evidence demonstrates diverse species of bacteria present in and around many human solid tumors. Some tumor-resident bacteria have been linked to inflammation, changes in the host immune system, and breakdown of chemotherapy drugs, all which can promote treatment resistance.
Many cancer patients routinely receive antibiotics during treatment because both disease and chemotherapy weaken the patient’s immune system, increasing infection risk. Grainger and colleagues assert that this clinical standard of care provides an opportunity to rationally study how antibiotic therapies could be used more intentionally to target bacteria residing within tumors and alter cancer therapy outcomes.
“Current anti-tumor treatments, including associated antimicrobial therapies, do not rationally consider the solid tumor microbiome as a target,” said Grainger. “Neither do oncologists routinely sample, profile or analyze a patient’s tumor microbial populations to formulate antimicrobial treatments currently prophylactically used to target more general systemic infection risks common to tumor patients.”
Ultimately, Grainger and his colleagues believe that more effective, rationally designed antimicrobial treatments — and, as a result, better cancer outcomes — for solid tumor patients hinge on reconsidering nanotech drug delivery systems with co-delivered or co-formulated antibiotics to address the tumor microbiome. The potential for the bacterial tumor microenvironment to neutralize chemotherapeutics requires further analysis.
“It will take many years to understand why these cancer nanotechnologies have minimal therapeutic efficacy, years that many tumor patients don’t have,” Grainger says. “Because both anti-tumor and anti-infection drugs are already clinically co-administered to patients currently in nanotechnology-free form, we’re advocating that these carrier-free formulations be more rationally directed now to consider the threat from tumor microbiomes. Hopefully, with this concept, we will see a change in patient outcomes for these difficult-to-treat solid tumors with miserable mortality stats and this will open opportunities for therapeutic re-designs downline.”