Discoveries

1. 2000: Gene Therapy Breakthrough with Rb2/p130

Key Findings:
Led by Dr. Antonio Giordano, this landmark study demonstrated the therapeutic potential of the Rb2/p130 tumor suppressor gene in vivo. Using a retrovirus vector, researchers delivered a functional Rb2/p130 gene into mice with induced lung tumors. A single injection resulted in significant tumor growth inhibition, showcasing the gene’s ability to restore cell cycle control and induce apoptosis (programmed cell death) in cancerous cells.

Revolutionary Impact:
This study was among the first to prove that gene therapy could be a viable strategy for cancer treatment. By directly targeting tumor-suppressor pathways, it paved the way for modern approaches in precision oncology, inspiring therapies that reactivate silenced tumor suppressors.

2. 2001: Dual Role of Rb2/p130 in Angiogenesis Inhibition & Discovery of CDK9/CDK10

Key Findings:
Dr. Giordano’s team revealed that Rb2/p130 not only suppresses tumor growth but also acts as a potent inhibitor of angiogenesis, the process by which tumors develop new blood vessels to sustain their growth. Additionally, the study identified CDK9 and CDK10, two cyclin-dependent kinases critical to cell cycle regulation and transcriptional control.

Revolutionary Impact:

• The anti-angiogenic role of Rb2/p130 opened doors to therapies targeting tumor vasculature, a strategy later refined in drugs like bevacizumab (Avastin).
• The discovery of CDK9 and CDK10 expanded understanding of cell cycle dysregulation in cancer. CDK9, in particular, is now a target in clinical trials for leukemia and solid tumors.

3. 2004: Discovery of Novel Structure Proteins (NSPs)

Key Findings:
Dr. Giordano’s team uncovered NSPs (Novel Structure Proteins), a family of proteins with unique structural roles in nuclear dynamics during cell division. Among these, Isoform NSP5a3a was found to be highly expressed in tumor cell lines, suggesting its potential as a diagnostic or prognostic tumor marker.

Revolutionary Impact:
NSPs provided new insights into mitotic errors and chromosomal instability in cancer. The identification of NSP5a3a as a biomarker laid groundwork for non-invasive diagnostic tools, enabling earlier detection of malignancies.

4. 2024: Synergistic Cancer Cell Death via Oleanolic Acid

Key Findings:
In a study published in the International Journal of Molecular Sciences, Dr. Giordano and Dr. Luigi Alfano demonstrated that oleanolic acid, a natural triterpenoid, potentiates the effects of the chemotherapy drug camptothecin. By modulating the DNA damage response, this combination increased cancer cell death in vitro while sparing healthy cells.

Revolutionary Impact:
This research highlights the potential of phytochemical-chemotherapy synergies to overcome drug resistance, a major hurdle in oncology. Oleanolic acid’s ability to enhance camptothecin’s efficacy offers a blueprint for developing lower-dose, high-impact regimens with reduced side effects.

5. 2024: Targeting Metabolic Vulnerabilities in Cancer

Key Findings:
In a recent study published in Nature (link), SHRO researchers identified a novel metabolic pathway exploited by aggressive tumors to sustain proliferation under hypoxic conditions. By inhibiting the enzyme PHGDH (phosphoglycerate dehydrogenase), the team disrupted serine biosynthesis, starving tumors of metabolites essential for survival.

Revolutionary Impact:
This work pioneers a new class of metabolism-targeted therapies, offering hope for cancers resistant to conventional treatments. PHGDH inhibitors are now in preclinical development, with potential applications in breast, pancreatic, and brain cancers.

6. 2024: Decoding Immune Evasion Mechanisms

Key Findings:
A study in the International Journal of Molecular Sciences (link) revealed how certain tumors exploit epigenetic reprogramming to evade immune detection. SHRO researchers identified a histone-modifying enzyme, KDM5B, as a key driver of immune suppression in melanoma.

Revolutionary Impact:
Targeting KDM5B with small-molecule inhibitors restored T-cell infiltration and enhanced checkpoint immunotherapy efficacy. This discovery bridges epigenetics and immunology, offering combinatorial strategies to reactivate the immune system against “cold” tumors.