Earlier today the prestigious journal Cancer Discovery published the results of our program’s latest work in mantle cell lymphoma. Although previous clinical trials have demonstrated the effectiveness of ibrutinib in treating patients with mantle cell lymphoma, researchers also noted that some patient’s lymphoma developed ibrutinib resistance during treatment. Our findings revealed some insight into why this resistance occurs and offers several potential treatment strategies for patients who develop ibrutinib resistance. Based on their findings,
“…the researchers devised two treatment strategies that they tested in lymphoma cell lines. Both involve serial use of two anti-cancer drugs — the first to weaken or “prime” the cancer cells, and the second to deliver an added impact. Both use the experimental agent palbociclib (which selectively inhibits two cell-cycle promoting proteins, CDK4 and CDK6) to slow down the cancer’s growth and sensitize cells to the killing power of a second drug.”
As the study’s lead researcher, Dr. Selina Chen-Kiang commented,
“While for many patients ibrutinib represents a valuable treatment option, it has limitations, and we have been able to demonstrate how novel therapy combinations that target the cancer’s resistance pathways might possibly work better.”
These results build on years of laboratory and clinical work at WCMC, and they highlight the need for further research such as our ongoing trial with ibrutinib plus palbociclib
If you have any questions please contact us and look to our clinical trials page for our ongoing trials.
For additional information see the press release from the American Association for Cancer Research.
Recently, at the 12th International Conference on Malignant Lymphoma, Dr. Peter Martin, presented preliminary results from a phase I study evaluating palbociclib (also known as PD 0332991) combined with bortezomib in patients with previously treated mantle cell lymphoma. Mantle cell lymphoma is characterized by genetic changes that result in loss of cell cycle control, resulting in unrestrained cell proliferation. Palbociclib is an oral drug that specifically inhibits CDK4, enzyme that is central to the proliferation of mantle cell lymphoma cells. Data from WCMC demonstrated that palbociclib could arrest the growth of mantle cell lymphoma cells and that prolonged growth arrest could sensitize the cells to killing by low doses of bortezomib, thereby potentially improving its efficacy and tolerability. In our recent oral presentation at the ICML, we reported that palbociclib could be safely combined with low-dose bortezomib and that the combination appeared to have promising efficacy. Our results suggest that strategies to control the cell cycle should be explored.
For a full listing of all current clinical trials underway in the Lymphoma Program, please click here.
In laboratory experiments, researchers at Weill Cornell Medical College have demonstrated that the cancer fighting effects of Velcade (bortezomib) and PD 0332991 were exponentially multiplied when used together in their laboratory studies on multiple myeloma tumor cells.
The normal cellular growth cycle is derailed in cancer. Uncontrolled growth and multiplication is often the result. The researchers found that PD 0332991 stops the cellular cycle in a vulnerable moment, leaving the cancer cell wide open for cellular destruction by Velcade.
The study, published online last month by the journal Blood, is the first to show that precise timing of therapies that target a cancer cell’s cycle — the life phases leading to its division and replication — disables key survival genes, resulting in cell death. The drug that delivers the weakening jab at the cell cycle is the experimental agent PD 0332991, which allows Velcade, a proteasome inhibitor already approved for use in myeloma and lymphoma, to land the final defeating blow at lower than normal doses.
Dr. Selina Chen-Kiang, professor of Pathology and Laboratory Medicine and of Microbiology and Immunology at Weill Cornell Medical College was the lead scientist on the study. In an interview Dr. Chen-Kiang said:
“Because robust functioning of the cell cycle is crucial to cancer growth and survival, this mechanism-based strategy could theoretically be used against many kinds of cancers.”
The same combination is being tested in patients with mantle cell lymphoma in a Weill Cornell investigator-initiated study led by Dr. John Leonard. Click here for more information about the mantle cell lymphoma study.