Cancer Pharmacology Lab

The challenge

Cancer is not a single disease, but many different diseases with their own risk factors, prognosis, survival rates and molecular underpinnings. Understanding these specificities and designing new therapies able to hijack cancer cells is extremely complex and require both a high-tech multidisciplinary approach and a translational one, based on a strict collaboration between pharmacologist, biotechnologists, oncologist and pathologists. Cancer is also a time-dependent disease, that can radically transform itself with time, becoming less and less responsive to therapies: this is why the future of cancer pharmacology is in early diagnosis and rational drug combinations.

Facing this challenge would be impossible without the active involvement of patients associations and the commitment of Foundations such as Fondazione Alessandra Bono, that continuously support our work.

Main research areas

Enhancing drug penetration in the neoplastic tissues

Drug concentration at the target tissue is a key determinant for any active drug. We are developing sensitive analytical methods based on mass spectrometry (MS) to measure the drug concentration in the whole tumor and even to visualize drug distribution in the tumor tissue (MS imaging). By applying these technologies, we want to investigate how new approaches, such as antibodies-drug conjugates and smart drug combination with distribution enhancers, can improve the penetration of anticancer agents.

Early detection of ovarian cancer

Ovarian cancer, in particular the high-grade serous (HGSOC) type, is characterized by poor prognosis, mainly due to advanced stage diagnosis. It has been proven that HGSOC cells from ovarian surface or Fallopian tubes reach the cervical canal at a very initial phase. We are developing a non-invasive test for early diagnosis of HGSOC based on the recognition, in the DNA retrieved from cervical smears, of tumor-specific molecular aberrations using innovative NGS techniques.

Improving therapeutic choices in ovarian cancer

PARP inhibitors have been recently introduced in the front line setting of HGSOC therapy, but only patients with tumors deficient in the homologous recombination pathway demonstrated a survival advantage. We want to develop an improved test for the selection at diagnosis of HGSOC patients that can benefit from PARP inhibitors. In parallel, we are investigating whether liquid biopsy can not only intercept the early onset of relapse, but also capture the major biological features of relapsed disease on which to base the therapeutic strategy.

Identifying new effective therapies for mesothelioma

Pleural mesothelioma is a rare cancer with few effective therapeutic options. Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields that recently proved to be effective against pleural mesothelioma in combination with chemotherapy. To enhance TTFields’ efficacy, we want to deeply understand their effects on cancer cells and tumor microenvironment, as well as their interaction with other anticancer drugs.

Optimizing the efficacy of marine-derived trabectedin against liposarcoma

The high activity of the marine natural product trabectedin against liposarcoma, which we discovered many decades ago and helped translate in the clinical setting, is related to its ability to induce adipocytic differentiation. Our preclinical evidence suggests that the combination of trabectedin and the PPAR_ϒ agonist pioglitazone activates adipocytic differentiation even in the case of liposarcoma that respond poorly to trabectedin. We want to optimize this combination and test its efficacy in the clinical setting.