Search IconSearch
January 21, 2015/Cancer/Research

Bringing Precision Medicine to Biliary Cancers

Program to study DNA, RNA alterations, test targeted therapies


By Alok Khorana, MD, and Davendra Sohal, MD, MPH


Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Biliary tract cancers – including intra- and extra-hepatic cholangiocarcinomas, and gallbladder cancer – are aggressive malignancies with poor clinical outcomes.

Most patients present with advanced disease, and current management options are limited to chemotherapy agents such as gemcitabine and cisplatin, with modest benefit.

In many other cancers, physician-scientists have been able to improve clinical outcomes by identifying molecular aberrations in tumors and by conducting clinical trials of novel therapies aimed at those molecular targets.

There are several obstacles, however, to studying biliary tract malignancies:

  • They are a group of relatively uncommon cancers.
  • Tissue biorepositories are rare or non-existent.
  • Federal funding for scientific research is limited.
  • Patients present late in the course of the disease, making enrollment in clinical trials difficult.

Surmounting the Obstacles to Biliary Cancer Research

At Cleveland Clinic’s Taussig Cancer Institute, we are building a research program to overcome these hurdles. With the family of Frank and Nancy Porter’s creation of the Porter Family Genomics Fund, we are able to initiate a comprehensive research program in biliary malignancies that will be quickly translatable into innovative clinical trials.

Our initial focus is the creation of a robust biorepository of tumor tissue specimens collected both retrospectively and prospectively from patients seen at Cleveland Clinic. We will utilize these biospecimens to develop an easily reproducible platform to study molecular alterations in biliary tract cancers.

Dealing with the Scarcity of Tumor Tissue Samples

In the past, we have been limited because traditional clinical specimens contain only small amounts of tumor tissue. Most diagnoses of biliary tract cancers are made using fine needle aspiration samples or bile duct brushings collected during procedures such as endoscopic ultrasound or endoscopic retrograde cholangiopancreatography.

Partnering with Case Comprehensive Cancer Center scientists who have extensive experience in clinical genomics, we have identified tumor sequencing platforms that can allow us to identify DNA and RNA changes in archived biliary tract cancer specimens obtained during routine clinical care. Our collaborators will use leading-edge high-throughput next-generation sequencing techniques and bioinformatics methods that can surmount the usual problems of quantity and quality of tumor tissue.


Next, we envision being able to correlate these molecular findings with clinical data to understand the impact of various molecular alterations on clinical outcomes. We are therefore also building a robust clinical dataset to complement potential molecular findings.

In addition, comparisons between biliary tract cancer specimens and non-neoplastic biliary tissues, such as specimens obtained during cholecystectomies, will allow us to further home in on alterations that play a critical role in cancer development and progression. Thus, we will be able to create a catalog of clinically relevant molecular alterations in biliary tract cancers.

Employing Clinical Trials of Targeted Therapies

Finally, we plan to apply this knowledge to clinical trials of novel targeted therapies. We already have a unique clinical genomics program at the Cancer Institute. As part of this program, we perform extended genomic sequencing of clinical specimens from patients with advanced solid tumors. Results are reviewed at a dedicated Genomics Tumor Board – a weekly meeting of clinical and translational oncologists.

Participants review each result in detail and make recommendations for targeted therapy – on-label drugs, off-label use or clinical trials – which are communicated to treating physicians.

We have a portfolio of clinical trials of targeted therapies encompassing many genomic alterations of known clinical value and many solid tumor histologies. We will build on our experience with this initial broad program, with a focus on obtaining novel agents and innovative trials specifically for our patients with biliary malignancies.

We are privileged to have the support of patient survivors and advocates such as Lisa Craine and her foundation, Craine’s Cholangiocarcinoma Crew.

Soon we hope to utilize modern tumor sequencing methods and novel targeted therapies in conjunction with a well-established program of patient identification, tumor sequencing, and coordinated patient access and enrollment into clinical trials of targeted therapies based on their individual tumor genome. This effort will bring individualized therapies and precision oncology to each of our patients with biliary malignancies.

Dr. Khorana is a staff member of Cleveland Clinic’s Department of Hematology and Medical Oncology and Director of the Taussig Cancer Institute’s Gastrointestinal Malignancies Program.

Dr. Sohal is a staff physician in the Department of Hematology and Medical Oncology and is the Director of the Taussig Cancer Institute’s Clinical Genomics Program.


Related Articles

Lung cancer cells
June 5, 2024/Cancer/Research
Impact of Tumor Burden on Survival for Patients with EGFR-Mutant NSCLC Treated with Osimertinib

Extent of baseline burden impacts progression-free and overall survival

cancer cells
June 4, 2024/Cancer/Research
Researchers Identify Tumor Microbiome Differences in Early- vs. Average-Onset Pancreatic Adenocarcinoma

Further study warranted to better understand the clinical implications of these findings

car T-cells
June 3, 2024/Cancer/Research
CAR T-Cell Treatment Offers Hope for Richter Transformation

Real-world study shows high response rates that are durable with commercial lisocabtagene maraleucel

Blood clot
May 17, 2024/Cancer/Research
Managing the Risks of Venous Thromboembolisms in Patients with Cancer

Oral anticoagulants may be beneficial but need to be balanced against bleeding risks

Doctors working on MGUS screening study
March 18, 2024/Cancer/Research
Pilot Study Aims for Early Identification of Multiple Myeloma Precursor Among Black Patients

First-of-its-kind research investigates the viability of standard screening to reduce the burden of late-stage cancer diagnoses

Physician with patient
March 6, 2024/Cancer/Research
Targeting Uncontrolled Erythrocytosis in Polycythemia Vera with Rusfertide

Study demonstrates ability to reduce patients’ reliance on phlebotomies to stabilize hematocrit levels

Doctor measuring patient's waist size
February 26, 2024/Cancer/Research
Impact of Obesity on GVHD & Transplant Outcomes in Hematologic Malignancies

Findings highlight an association between obesity and an increased incidence of moderate-severe disease

Physician with patient
February 21, 2024/Cancer/Research
Strategies for Improving Clinical Trial Equity

Cleveland Clinic Cancer Institute takes multi-faceted approach to increasing clinical trial access