Bentham Science Newsletter

Oncology Spotlight

News about Cancer Research.

Oncology Spotlight | Bentham Science

In this issue, we take a look at some recent cancer research news.

Tracing the Origins of Breast Cancer: Genetic Mutations in Healthy Cells

A groundbreaking study led by researchers from the University of British Columbia and collaborators has identified cancer-like mutations in the healthy breast cells of women, offering insights into the early genetic origins of breast cancer. Using advanced single-cell gene sequencing, the team analyzed over 48,000 breast cells from 28 women without cancer. Approximately 3% of luminal cells, which line milk ducts and lobules, exhibited genetic alterations associated with cancer, specifically copy number alterations—duplications or deletions of large DNA segments.

These findings suggest that these silent mutations may serve as early building blocks for breast cancer development. The study also highlighted that some women with BRCA1/BRCA2 genetic variants carried cells with multiple mutations, pointing to a potential progression pathway.

This research emphasizes the importance of understanding early mutations to develop better cancer prevention, monitoring, and treatment strategies, potentially transforming how cancer risk is managed in high-risk individuals.

These results are complemented by another recent study from the University of Texas MD Anderson Cancer Center. This research sheds more light on early genetic abnormalities in breast tissue. This research revealed that 3% of breast epithelial cells from healthy women displayed chromosomal abnormalities, a condition known as aneuploidy, which is typically associated with invasive breast cancer. These aberrant cells accumulate and expand with age, raising critical questions about how "normal" tissues are defined and how breast cancer originates.

Interestingly, these chromosomal changes, such as gains in chromosome 1q and losses in 10q, 16q, and 22, resemble those seen in invasive breast cancer, highlighting their potential role as precursors. The researchers also found that different cellular lineages in the mammary gland exhibited unique genetic profiles, possibly reflecting distinct origins for estrogen receptor-positive and negative breast cancers.

Together, these findings emphasize the need for more advanced diagnostic approaches to differentiate benign anomalies from cancer, offering new avenues for understanding and potentially preventing breast cancer.

Targeting Tumors with Copper Deprivation: A New Cancer Therapy

Researchers at the Max Planck Institute for Polymer Research, in collaboration with Stanford University and Goethe University, have developed an innovative method to combat cancer by disrupting copper homeostasis. While copper is vital for healthy cell function, cancer cells require significantly higher amounts to sustain their rapid growth. By depriving tumor cells of copper, this method effectively kills them without harming healthy cells.

The approach – dubbed a “copper withdrawal” – utilizes nanofibers made from copper-binding peptides, derived from the Atox1 chaperone protein. These nanofibers are engineered to enter tumor cells and bind copper ions with high affinity, even outcompeting natural copper-binding biomolecules. This depletion of copper disrupts redox equilibrium in cancer cells, inducing oxidative stress and cell death. Laboratory tests on breast cancer cell cultures showed an 85% reduction in tumor cells within 72 hours, while healthy cells remained unaffected.

This groundbreaking research offers hope for future therapies targeting copper metabolism as a novel avenue in cancer treatment.

Engineered Bacteria Offer Hope for Personalized Cancer Vaccines

Researchers at Columbia University have developed a bacterial vaccine that leverages the natural tumor-targeting properties of probiotics to train the immune system to identify and destroy cancer cells. This personalized immunotherapy encodes tumor-specific proteins called neoantigens, enabling the immune system to precisely attack cancer cells while leaving healthy tissues unharmed. The system also overcomes tumors' immunosuppressive mechanisms, enhancing its effectiveness.

In mouse models of advanced colorectal cancer and melanoma, the bacterial vaccine successfully suppressed tumor growth and, in some cases, completely eliminated primary and metastatic cancers. It also prevented cancer recurrence in treated mice, suggesting potential for long-term remission in patients. This approach, which delivers high concentrations of immunomodulatory compounds directly to tumors, addresses challenges faced by earlier cancer vaccines by modulating the tumor environment locally.

This personalized treatment could be rapidly manufactured using bioinformatics to identify patient-specific tumor markers, offering a safer, more effective, and customizable cancer therapy. Researchers are optimistic about advancing to human trials.

Iron from Red Meat Linked to Colorectal Cancer Development

Researchers from the Institute for Biomedical Sciences at Georgia State University have identified a mechanism that explains how consuming red meat can increase the risk of colorectal cancer. The study, published in PNAS, shows that heme, a type of iron found in red meat, interacts with gut bacteria to produce harmful metabolites that promote cancerous cell growth.

Heme iron breaks down into metabolites that damage the gut lining, triggering inflammation and creating an environment conducive to cancer development. The researchers used mouse models and human cell studies to confirm the connection. A Western-style diet high in red meat was shown to amplify these effects, with heme-driven metabolites directly transforming gut stem cells into cancerous cells.

This discovery highlights the role of diet and gut bacteria in colorectal cancer, offering potential new avenues for prevention and treatment. The study underscores the importance of moderating red meat consumption and further exploring dietary factors in cancer prevention.

The role of gut microbiota in colorectal cancer progression is also notable in diets high in red meat. Dysbiosis, or an imbalance in gut microbes, often results from diets high in red meat and low in fiber, exacerbating the production of pro-carcinogenic metabolites. Specifically, these metabolites can alter the gut's immune environment, increase oxidative stress, and damage DNA, further elevating cancer risk. While read meat is healthy for the body, it’s worth reducing red meat intake and incorporating fiber-rich foods in the diet. Research suggests that this reduction could mitigate harmful gut bacterial interactions and lower the risk of disease progression.

Microbiota: Cancer's Double Agents

The intricate relationship between microbiota and cancer reveals both risk and opportunity. Certain microbes, like Helicobacter pylori and Fusobacterium nucleatum, are linked to cancer progression by fostering chronic inflammation and producing carcinogenic by-products. These harmful bacteria have been associated with gastric, colorectal, and oral cancers, highlighting microbiota's potential role as a cancer promoter.

Conversely, the same microbial ecosystem offers promising avenues for cancer management. Emerging therapies use probiotics, prebiotics, and genetically engineered bacteria to enhance immune responses, reduce chemotherapy toxicity, and target tumors with precision. Inspired by historical breakthroughs like Coley’s bacterial vaccine, modern science is now leveraging microbiota to improve cancer treatments.

Ongoing clinical trials aim to validate these microbial-based therapies, offering hope for innovative and less toxic cancer treatments. Microbiota, once seen as a villain in malignancy, is proving itself a vital ally in the fight against cancer. Learn more about the role of gut microbiota in cancer therapy in this Current Cancer Drug Targets review.

Scientists glue two proteins together, driving cancer cells to self-destruct

Stanford Medicine researchers have developed a novel cancer treatment by leveraging apoptosis, the body’s natural cell death process, to target lymphoma cells specifically. The team created a molecule that connects two proteins, BCL6 and CDK9, triggering cell death genes that lymphoma cells typically suppress. Unlike conventional therapies that inhibit cancer-promoting mechanisms, this approach flips the script by using cancer’s reliance on BCL6 against it, forcing the tumor cells to self-destruct.

The molecule has shown remarkable specificity in lab tests, killing only diffuse large B-cell lymphoma cells without harming other cell types. Additionally, it activates multiple cell-death signals simultaneously, potentially reducing the risk of treatment resistance. Initial tests in mice showed no significant side effects, and researchers are now exploring its efficacy in living animal models.

This innovative strategy, supported by Stanford's SPARK program and the NIH, could pave the way for targeted therapies that exploit cancer’s vulnerabilities while sparing healthy tissue.

A Look at Gender Influence Immunotherapy Outcomes in Lung Cancer?

Recent research sheds light on sex-based differences in immunotherapy outcomes for patients with advanced non-small cell lung cancer (NSCLC). Researchers at Careggi University Hospital, Florence, analyzed data from 99 patients treated with PD-1 immune checkpoint inhibitors (ICIs) nivolumab and pembrolizumab for this study. Results revealed that male patients exhibited a slight trend toward improved progression-free survival (PFS) compared to females, particularly with nivolumab. However, overall survival (OS) showed no significant difference between genders. Disease control rates were higher in males (55.7%) than females (45.7%), though not statistically significant.

The findings underscore biological and hormonal factors contributing to immune function and cancer outcomes, such as sex hormone modulation of the PD-1/PD-L1 pathway. While current immunotherapy strategies do not yet consider gender differences, the study advocates for future clinical trials with equal gender representation to optimize personalized cancer treatments.

These insights highlight the potential for integrating gender-specific approaches into oncological care, improving outcomes for all patients/