NFCR Basic Research in Action: Drug Resistance

Sometimes cancers are inherently unaffected by a specific drug and sometimes drug resistance occurs when cancers that have been responding to a therapy suddenly begin to grow again. In that latter case, the cancer cells resist the effects of treatment and the therapy being used will need to be changed.

Research is underway to investigate ways of reducing or preventing cancer drug resistance.

Dr. Wei Zhang’s research addresses the variability in cellular properties, within and across cancer types, which often leads to treatment resistance and poor survival in patients. For example, in non-small lung cancer (NSCLC) patients, his team identified a cell population that contributes to drug resistance. Potential therapy to change these cells offers great promise to enhance treatment approaches for patients.

Dr. Rakesh Jain’s research is focused on combining anti-angiogenic treatment (normalize a tumor’s abnormal blood vessels) with the immunotherapy of immune checkpoint inhibitors to enable the inhibitors to effectively fight GBM.

The new immunotherapy called checkpoint inhibitors—that unleashes the brake on our immune system to recognize and fight cancer cells—is successful in some cancers but not in treating GBM.  His lab has previously shown and is renowned for the concept that a disturbed balance of blood vessel growth factors in tumors results in abnormal tumor vessels that cause a lack of oxygen and immunosuppression. If this research is successful, the results will directly inform the design of clinical trials testing their novel treatment strategies to overcome resistance to checkpoint inhibitors.

Dr. Susan Horwitz, a molecular pharmacologist who studies how drugs work in the body, discovered how the drug, Taxol, works inside cells to halt cell division. Millions of cancer patients have been treated with Taxol. NFCR’s long-term funding for her research helped to further our understanding of the resistance problem that patients develop with Taxol. NFCR funded a collaboration between Dr. Horwitz and chemist, Dr. Amos B. Smith, III, to develop new drugs similar to Taxol that may overcome the drug resistance problem experienced by patients with triple negative breast cancer, and lung, ovarian, and pancreatic cancer.

Dr. Daniel Haber believes the circulating tumor cells (CTCs) shed from a primary and metastatic tumor sites and travel through the bloodstream, hold the key to predicting cancer treatment response, resistance and cancer relapse. The CTC-iChip device developed by his team captures the few CTCs among millions of healthy blood cells in a patient’s blood sample. With culturing of the CTCs to increase their numbers, genetic testing and other tests can be conducted on the cells.  DNA mutations can be identified that may be causing the cancer cell’s resistance to treatment. The CTC-iChip is currently in use in hospitals worldwide for research purposes. Soon it will be submitted to the FDA for required approval for doctors to obtain the critical information they need for important life-saving treatment decisions for their patients.