Dr. Cora Sternberg is an American oncologist who trained at the Memorial Sloan Kettering Cancer Center in New York and was the Chief of Medical Oncology in one of Italy’s largest public hospitals in Rome. She sought to maintain the highest level of patient care through clinical research and education in Italy. Research funding has been a serious problem for many Italian scientists, creating a widely acknowledged “brain drain” among researchers who leave to find funding for their work in other countries, most notably the United States. Funds often go to only a few Italian research centers.

For this reason, Dr. Sternberg founded the Samuel and Barbara Sternberg Cancer Research Foundation –ONLUS (in her parents’ names) which was recognized by the Italian government in 2004. Since then, she has been raising funds on her own, with the help of her patients and friends, to support cancer care and research in Italy.

Dr. Sternberg is highly respected internationally for her scientific and organizational capacities. For this reason, she was an elected Officer to the Executive Board of the European Organization for Research and Treatment of Cancer (EORTC), has been nominated by the American Society of Clinical Oncology (ASCO) to chair their scientific programs and was responsible for Genitourinary Cancer education for the European Society of Medical oncology (ESMO) for many years. In November 2018, she transferred to become the Clinical Director of the Englander Institute for Precision Medicine and full Professor of Medicine at Weill Cornell University in New York.

Dr. Sternberg believes that this foundation can make a difference in Italy and worldwide and that she has the track record, reputation, and energy to prove it.

Dr. Sternberg has made significant contributions to the treatment of cancer, particularly genitourinary cancers. She is best known for her seminal work performed at Memorial Sloan Kettering Cancer Center in New York in developing the M-VAC chemotherapy regimen. This has become the gold standard of treatment for more than 20 years for bladder and urothelial cancers and has saved lives and decreased pain and suffering in patients worldwide. Since then, Dr. Sternberg has become internationally recognized for her research in bladder preservation in patients with muscle infiltrating bladder cancer who would otherwise have had to remove their bladders.

Dr. Sternberg has made significant contributions to the treatment of cancer, particularly genitourinary cancers. She has been responsible for developing chemotherapy regimens in bladder cancer that are today considered the standard of care worldwide, M-VAC and High dose or dose dense M-VAC (HD-MVAC, DD-MVAC). HD-M-VAC is primarily used in the neo adjuvant setting and is currently the subject of a SWOG ongoing study and was presented as superior to GC therapy at ESMO in 2021.

While at San Camillo, she has published on behalf of the EORTC and several large cooperative groups, the largest randomized adjuvant chemotherapy bladder cancer trial to date. “Immediate Versus Deferred Chemotherapy after Radical Cystectomy in Patients with pT3-pT4 or N+ M0 Urothelial Carcinoma of the Bladder (EORTC 30994): An Intergroup, Open-Label, Randomised Phase 3 Trial. This trial demonstrated the value of adjuvant chemotherapy after cystectomy. A meta-analysis showed that overall, there is an OS benefit of immediate adjuvant chemotherapy, especially with cisplatin-based combination therapy. She has taken part in a recent international collaborative update with the MRC in an individual patient meta-analysis, has corroborated these results.

At San Camillo, together with investigators in her department, Dr. Sternberg has collaborated with the RISC (Retrospective International Study of Cancers of the Urothelial Tract) investigators to create a large data base (n=3024). Several publications have emerged, also from Rome, Italy using his database on neoadjuvant vs. adjuvant chemotherapy.

San Camillo was the highest contributor to the SAUL study, an extended access program of atezolizumab, a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1) in patients who have received prior chemotherapy and who were ineligible for the prior registration studies (poor real function, inflammatory disease etc), demonstrating that this regimen can be safely administered to these patients.

Dr. Sternberg was an author on the practice changing phase III study of Pembrolizumab as 2nd line therapy after failure of platinum-based therapy vs chemotherapy (investigator’s choice). Urothelial Cancer patients have also now started receiving second-line treatment with immunotherapeutic agents. We have been part of this study in Italy at San Camillo Hospital, the KEYNOTE-045 trial and have recently studied a patient with an exceptional response to immunotherapy. The patient received treatment for 2 years per the protocol and was monitored using serial CT scans. The patient has been free of disease for over 6 years and is currently off all therapy and is followed by colleagues in Milan.

The utilization of immune checkpoint inhibitors (ICIs) will only increase for UC, and as such, understanding the molecular mechanisms of response to immunotherapy is essential for developing more effective treatments for UC patients. Bagaev et al. previously reported the development and utilization of a Molecular Functional (MF) Portrait to dissect genomic and transcriptomic features of tumors, including bladder cancer. Therefore, we comprehensively characterized the patient’s tumor and tumor microenvironment (TME) using the MF Portrait. Briefly, the analysis showed the presence of the APOBEC signature, a high TMB, and the ATM mutation in the patient’s tumor. Our integrated genomic and transcriptomic analysis revealed important insights that can eventually lead to the development of clinically useful biomarkers. In June 2022 we have submitted a manuscript on this exceptional responder with Italian and American authorship.

Patients with muscle invasive bladder cancer are usually treated with platinum-based chemotherapy and radical cystectomy. We have patients who have undergone chemotherapy in Italy at San Camillo and at the Vincenzo Pansadoro Foundation who have had a complete response to chemotherapy on subsequent Transurethral resection of then bladder (TURB). We have collected these cases and reviewed their pathology and are planning to study them with clinical whole genome sequencing (cWGS), RNA sequencing and spatial transcriptomics, to map the spatial architecture of the cells and how it talks to and interacts with its surroundings. These cases will be compared to cases who have undergone cisplatin-based chemotherapy and radical cystectomy and have still had muscle invasive disease after chemotherapy. We will try to detect differences in those who respond well to chemotherapy, in theory being able to avoid chemotherapy in those who do not respond.

While at San Camillo, Dr. Sternberg has been a Principal Investigator on the Javelin Bladder 100 trial with avelumab maintenance therapy that has changed clinical practice guidelines worldwide in patients who have responded to first line platin based combination therapy. She has also been on the steering committee and recently published the STRONG study with durvalumab, a monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1), in pre-treated bladder cancer patients. Dr. Sternberg is on the steering committee of a study with Sacituzumab Govitecan (anti-Trop-2-SN-38 ADC), a first-in-class antibody-drug conjugate. This work has also recently been published and this drug now has accelerated approval in the US.

Dr. Sternberg has established a collaboration with the Bladder Cancer Advocacy Network (BCAN) and the Hoosier Cancer Oncology Group to perform whole genome sequencing (WGS) on their large cohort of bladder cancer patients.

She is actively involved in treating patients with both early and advanced prostate cancers with new and experimental therapies. She has been intimately involved in developing studies that have led to the registration of abiraterone acetate and enzalutamide, as well as other novel therapies for prostate cancer. Abiraterone was approved in the USA the day after the FDA inspection at San Camillo in Italy. She is the Principal investigator and senior author of the PROSPER phase III study of enzalutamide in patients with non-metastatic castration resistant prostate cancer (M0 CRPC), published in the NEJM and approved by the FDA and EMA due its decrease of > 70% in metastases free survival that was associated with a statistically significant 27% reduction in the risk of death, a clear improvement in overall survival, improvement in QoL and decrease in the time for the need of other antineoplastic therapy. This is an important practice changing study!

While at San Camillo, the team participated in the COMIT I cabozantanib study (a small molecule inhibitor of the tyrosine kinases c-Met and VEGFR2). They have studied the combination of abiraterone and an AKT inhibitor, ipatasertib that was published in the Lancet. Dr. Sternberg was on the steering committee for the CARD study, which established sequencing in mCRPC.

She has also been instrumental in developing darolutamide, a novel AR inhibitor for patients with prostate cancer. The ARASENS triplet therapy for patients with metastatic hormone sensitive prostate cancer is a practice changing study that was published in the New England Journal of Medicine.

While at San Camillo, her team collaborated with investigators at the John’s Hopkins University to validate a test for ARV-7 splice variants in circulating tumor cells (CTCs) in patients with CRPC and worked closely with them on several academic studies.

Dr. Sternberg is currently conduction a study on the Molecular Basis of Lineage Plasticity and AR-Independent Prostate Cancer. Lineage plasticity has emerged as an important mechanism of treatment resistance in prostate cancer. Treatment refractory prostate cancer is associated with loss of luminal prostate markers and neuroendocrine/neuronal features. Clinically, lineage plasticity may manifest as low prostate specific antigen (PSA), resistance to AR pathway inhibition, and small cell/neuroendocrine pathologic features. Neuroendocrine prostate cancer has been described as a rare subset of prostate cancer. However, it is increasingly acknowledged that many prostate adenocarcinomas may eventually evolve into neuroendocrine carcinomas, which may contribute to hormone refractoriness and rapidly progressive tumor behavior. The median survival for cases of metastatic neuroendocrine prostate cancer is less than one year. Understanding its biology and growth control mechanisms that result in loss of AR signaling dependence is crucial in developing more effective therapies.

Biomarkers such as p53 are often altered in blood as is RB in tissue specimens. The goal of this study is to evaluate alterations in p53 in blood and PTEN and RB in tissue specimens and determine their association with overall survival. The goal of this study is to analyze fresh frozen and formalin-fixed paraffin-embedded pathologic tissues as well as blood samples, from subjects with suspected neuroendocrine prostate cancer and to determine the association of these biomarkers with overall survival. Any subjects that have or who are suspected to have neuroendocrine prostate cancer or poorly differentiated prostate cancer are eligible for this study. Exploratory Objectives: Molecular assays will be performed on archival or fresh frozen material and blood, and will include but not limited to: Expression profile analysis of RNA extracted from fresh frozen or paraffin embedded tumor tissue or circulating tumor cells utilizing next generation RNA sequencing platforms as well as tissue microarrays. Molecular analysis of tissue and/or circulating tumor cells for protein expression; cell free DNA (cfDNA) and/or RNA. Single cell sequencing of tumor and/or stroma cells. Mass cytometry and spatial transcriptomics analysis of tissue. The association of any molecular analysis may be evaluated for an association with overall survival and clinical parameters. All samples will be de-identified.

She has been involved in developing Prostate Cancer Working Group (PCWG2 and PCWG3) and now is working on PCWG4 that are guidelines for academicians in evaluating prostate cancer patients in clinical trials. Most recently, she has obtained grant support to study the genomics of African American men with prostate cancer. She is also a collaborator on genomic studies with the National Cancer Institute (NCI) in the US.

In addition, Dr. Sternberg has become increasingly known for her research and use of novel molecularly targeted agents in the treatment of renal cell carcinoma. Dr. Sternberg coordinated a renal cell cancer study that led to approval of pazopanib in Italy and the US of a molecular targeted agent against endothelial vascular growth.

Dr. Sternberg is also conduction a study on multiomics profiling study to classify the origin of Cancers of Unknown Primary (CUP). Cancer of unknown primary (CUP) is a relatively common disease that accounts for about 9% of all cancer diagnoses. The prognosis is poor and median survival is approximately 9 months. A classifier of cancer type based on a multiomics profiling approach (e.g. RNA-seq, DNA methylation signatures) may show a high specificity, sensitivity, positive predictive value and negative predictive value of the original primary site of tumor. Patients with a more specific diagnosis who receive a tumor type-specific therapy should show improved overall survival compared with patients who receive empirical therapy. This profiling will be complemented with other next-generation sequencing assays including whole exome sequencing (WES). This is a pilot study to classify the origin of cancers of unknown primary (CUP). DNA and RNA (and WES tumor profiling in some cases) will be evaluated. If a tumor origin of origin is identified with high likelihood, patients will be treated accordingly.