Chong-xian Pan: Revolutionizing cancer care
The era of the Human Genome Project has given rise to a new field called molecular oncology that promises to dramatically improve cancer screening, diagnosis and treatment.
“We are using state-of-the-art molecular methods to develop cancer-specific molecules that will revolutionize all aspects of cancer care,” said Chong-xian Pan, a molecular oncologist and UC Davis associate professor of hematology and oncology.
Pan and his colleagues are designing molecules that will behave like tiny guided missiles, seeking out cancer cells to deliver a variety of useful payloads. Among them are molecules that carry contrasting agents for non-invasive imaging of the bladder, fluorescent molecules that allow direct visualization of cancer during surgery and lethal drugs to kill cancer and cancer stem cells that cause deadly metastasis.
Pan has focused much of his work on the diagnosis and treatment of bladder cancer, the fourth most common cancer in males and ninth most common in females.
“Most bladder cancer is diagnosed in its very early stages,” Pan said. “But diagnosing, treating and following up the cancer can be painful and expensive. It involves looking directly inside the bladder using a cystoscope, a thin, lighted instrument.”
The molecules Pan is developing promise to decrease the need for cystoscopy by linking a contrasting agent to a bladder cancer-targeted molecule. This will allow the use of non-invasive imaging methods, like MRI or ultrasound, to be used to look for cancer inside the bladder.
Pan has found several promising candidate molecules and expects clinical trials in patients to begin in the next year or two. Once the molecule proves to be effective, he will then work to link it with chemotherapy drugs to it as a way of improving treatment.
“Chemotherapy is widely used to treat cancer, but about half the patients with bladder cancer do not respond to chemotherapy. We are trying to identify which patients will not respond to chemotherapy and which will,” Pan explained.
As a result, Pan has teamed up with Paul Henderson, assistant professor at UC Davis, and collaborators at Lawrence Livermore National Laboratories (LLNL) to apply technology similar to that used to date fossils to monitor damage to DNA caused by chemotherapy.
In one study, Pan attached an isotope of naturally occurring carbon – called 14C – to a commonly used chemotherapy drug called carboplatin. Using a technology called accelerator mass spectrometry (AMS) only available at facilities like LLNL, Pan and his collaborators measure DNA damage by looking for 14C in the DNA of treated patients.
“Because of the high sensitivity of AMS, chemotherapy-induced DNA damage can be detected and we can infer resistance to chemotherapy,” said Pan. “This method will ultimately allow physicians to design personalized chemotherapy.”
One of the most important recent discoveries in cancer research has been the revelation that many types of cancer originate from and spread via cancer stem cells (CSCs). So far, however, none of the chemotherapy drugs targets CSCs. Pan is working to screen billions of molecules looking for a way to target the CSCs involved in leukemia. This research is in its early stages, but Pan is confident that targets will be found and CSC-specific molecules will be able to cut the cancer off at the root.
“We have had great success so far with these methods. It’s very exciting for us and for the future of cancer treatment,” Pan said.