All-female team explores a promising compound against this 鈥榚ssentially incurable鈥� disease
Society has no shortage of metaphors for cancer. Oncologist Siddhartha Mukherjee famously titled his bestselling book after a 19th-century surgeon鈥檚 note referring to cancer as 鈥渢he emperor of all maladies, the king of terrors.鈥�
Closer to home, marine scientist Dr. Gisela P. Concepcion has her own uniquely harrowing metaphor. 鈥淐ancer is a colonizer,鈥� she says. 鈥淲hat happens is almost like a geographic colonization to steal resources.鈥�
Concepcion describes metastasis, the process by which cancer cells break away from their primary tumor and multiply in other organs. A biochemist by training, she has dedicated her career to discovering marine-derived natural products鈥攃hemical compounds from sea-dwelling organisms like invertebrates鈥攖o develop drugs that can combat deadly diseases, including metastatic breast cancer.
With this goal in mind, Concepcion and an all-female research team from the 天美视频 Marine Science Institute (UP MSI) recently published a study on the promising activity of a potent compound derived from the Philippine blue sponge (Xestospongia sp.) against metastatic breast cancer in mice.
The team, composed of Concepcion, Dr. Lilibeth Salvador-Reyes, Zildjian Acyatan, Shalice Susana-Guevarra, Myra Ruth Picart, and Eliza Belen, demonstrated that the compound renieramycin M (RM), especially when combined with the clinically used cancer drug doxorubicin (Dox), significantly shrank tumors in mice while reducing the toxicity commonly associated with chemotherapy drugs.
These findings are timely. A World Health Organization (WHO) report states that 2.3 million people, mostly women, were diagnosed with breast cancer in 2022. The Philippines has one of the highest breast cancer incidence rates in Asia. In a 2023 forum, Philippine Cancer Society President Dr. Corazon Ngelangel noted that around 65% of breast cancer cases in the country are diagnosed at an advanced or metastatic stage.
The five-year survival rate for metastatic breast cancer averages around 44%, making it the second leading cause of cancer-related deaths worldwide鈥攁 true 鈥渜ueen of terrors.鈥�
The problem with existing treatments
The so-called 鈥渃olonization鈥� of cancer cells begins with a genetic mutation. A single mutation, Concepcion explains, can cause a normal round breast cell to develop 鈥渓ittle legs or spikes,鈥� enabling it to move and penetrate the extracellular matrix. Once inside blood vessels, these mutated cells travel to other organs, where they consume nutrients and establish new tumors.
鈥淭he speed at which this happens means scientists are in a constant arms race against an insatiable invader,鈥� Concepcion says. 鈥淏ut the work is not fruitless.鈥�
Natural products have led to the development of therapies such as doxorubicin, which originates from a fungus-like bacterium found in the Adriatic Sea. The fact that RM pairs well with doxorubicin in laboratory studies is cause for optimism. However, no single therapy is a cure-all.
For breast cancer treatment, affordability often dictates options. Patients with limited financial means are typically prescribed cyclophosphamide, a DNA strand breaker that lacks specificity, killing both cancerous and healthy cells. Many patients succumb not just to cancer but also to compromised immune systems caused by the drug.
Taxol, derived from the endangered Pacific yew tree, is an effective yet prohibitively expensive option. It targets microtubules essential for cell division but can be rendered ineffective by drug-resistant cancer cells that expel it using efflux pump proteins.
Doxorubicin, a more accessible option, functions as a DNA intercalator and blocks an enzyme essential for cancer cell replication. However, it has serious drawbacks, including cardiotoxicity and a risk of inducing leukemia due to its DNA-altering properties.
鈥淒oxorubicin alone is not very potent,鈥� Concepcion explains. 鈥淚ts inhibitory dose in cells is at the low micromolar level, meaning patients require high doses, increasing the likelihood of severe side effects.鈥�
Testing a new approach
The team suspected that RM, which independently triggers programmed cell death in cancer cells, could work synergistically with doxorubicin to enhance its cancer-fighting effects. Previous in vitro studies supported this theory, but further testing was needed in living organisms.
For their study, the team purified RM using a method developed by their collaborators from Chulalongkorn University and Meiji Pharmaceutical University. They obtained doxorubicin commercially and used 4T1 mouse mammary tumor cells, a well-established model for advanced-stage, triple-negative human breast cancer.
Triple-negative breast cancer, common in women under 40, lacks certain receptors found in other breast cancers, making it more aggressive and difficult to treat.
Following strict animal-care protocols, the researchers injected mice with 4T1 cells and tested different doses of Dox and RM, both individually and in combination. Tumor growth was monitored daily for a month.
Their findings were significant. A combination of Dox (5 mg/kg) and RM (1 mg/kg) reduced tumor size by 46.53% by day 21, outperforming other treatment groups, including those receiving Dox or RM alone.
Histopathological analysis revealed that the same Dox-RM combination reduced liver metastases by 86.36%, compared to 76.04% for RM alone and 75.33% for a lower-dose Dox-RM mix (5 mg/kg + 0.2 mg/kg).
To assess drug toxicity, the team tracked the mice鈥檚 weight, behavior, and lifespan. High doses of Dox and RM alone resulted in the highest fatality rates. However, the combination therapies鈥攑articularly Dox (5 mg/kg) + RM (1 mg/kg) and Dox (5 mg/kg) + RM (0.2 mg/kg)鈥攕howed lower toxicity. The latter had no recorded fatalities, while the former had only one, which occurred late in the experiment (day 33). In contrast, fatalities in the high-dose Dox group began much earlier.
A step forward in cancer research
The study demonstrates that RM, especially when combined with Dox, could be a promising treatment option for metastatic breast cancer. By enhancing efficacy while reducing toxicity, RM-Dox combinations may pave the way for more effective and less harmful therapies.
The researchers emphasize that while their findings are promising, further studies, including clinical trials, are necessary before RM-based treatments can be used in human patients.
For now, the fight against breast cancer continues. But thanks to the work of Concepcion and her team, science is one step closer to a new weapon in the battle against this relentless disease.
Read the team鈥檚 paper .
Read the in vitro study let by Jortan Tun and including some of the same authors .
Read the Open Sea Farming Protocols for the Philippine Blue Sponge made by the MSI .
