Through a collaboration between researchers at Weill Cornell Medical College, Memorial Sloan-Kettering, and the National Cancer Institute, researchers have reported that a tumor-targeting compound called PU-H71 can reveal with great accuracy the set of altered pathways that contribute to malignancy, thus allowing physicians to “fish-out” entire networks of abnormal proteins in tumor cells.
One major obstacle in the fight against cancer is that anticancer drugs often affect normal cells in addition to tumor cells, resulting in significant side effects. Yet research into development of less harmful treatments geared toward the targeting of specific cancer-causing mechanisms is hampered by lack of knowledge of the molecular pathways that drive cancers in individual patients.
“A major goal of cancer research is to replace chemotherapy with drugs that correct specific molecular pathways disrupted by cancer,” said Weill Cornell’s Dr. Ari Melnick, one of the study’s lead investigator. The research was published in Nature Chemical Biology.
The researchers have uncovered that PU-H71 can reveal, with great accuracy, the set of altered pathways contributing to malignancy, thus allowing physicians to “fish-out” entire networks of abnormal proteins in tumor cells. PU-H71 binds to these abnormal protein complexes which are part of protein networks supporting cancer cell growth, division and survival. This knowledge could lead to more targeted, effective and individualized therapies for the personalized treatment of cancer – a disease in which no two tumors are alike – while producing fewer side effects and ultimately sparing patients from undergoing chemotherapy.
Based on these findings Dr. Melnick and colleagues have received a multi-investigator collaborative grant from the National Cancer Institute in support of clinical trials for the treatment of cancer. Currently, patients are being recruited for the first clinical trial to test the safety of PU-H71 as a drug used for the treatment of a variety of tumors. Subsequent trials will include patients with cancers such as breast, lymphomas, and chemotherapy-resistant leukemia.
By Peter Martin, MD
Investigators at Fred Hutchinson Cancer Research Center in Seattle recently reported the results of retrospective study of 118 patients with mantle cell lymphoma. After receiving a variety of first-line chemotherapy regimens, including R-HyperCVAD and R-CHOP, 85 patients underwent consolidation with autologous stem cell transplantation. Initially, it appeared that patients who received an aggressive induction regimen, like R-HyperCVAD, had a better outcome following stem cell transplantation. Interestingly, after controlling for other prognostic factors, like age, LDH, White Blood Cell count, and performance status, it became apparent that choice of induction chemotherapy had little effect on outcome after transplant. In other words, patients that had a better baseline prognosis were more likely to be treated with aggressive first-line regimens, which gave the appearance that the more aggressive regimens were responsible for better outcomes. Click here to read the abstract.
This study is important because it helps us to contextualize the results of many of the phase 2 studies that have been published on mantle cell lymphoma. It is possible that the results of phase 2 studies appear to be more or less impressive than standard therapies because there is no comparison group; i.e., it is the baseline prognostic factors of the patients that explain the results rather than the treatment regimen being tested. Retrospective studies, such as the study from Seattle, are also prone to bias because it is difficult to control for everything, particularly prognostic factors that we don’t yet know about. That is why randomized studies comparing at least two regimens are of critical importance. Only randomized studies can distinguish the between the good and bad effects of two or more regimens. Continue reading “Lymphoma in the News: Choice of Pre-Transplant Chemotherapy Regimen May Not Be As Important As Other Factors in Mantle Cell Lymphoma”
Weill Cornell’s Dr. Rebecca Elstrom attended the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland and provides this update:
Maintenance rituximab improves progression free survival in patients with mantle cell lymphoma when given after rituximab in combination with chemotherapy. These results were reported at the 11th International Conference on Malignant Lymphoma this week. Dr. Kluin-Nelemans and colleagues compared R-CHOP chemoimmunotherapy to R-fludarabine/cyclophosphamide as first line treatment of patients over 60 with mantle cell lymphoma, finding R-CHOP to be superior in this group of patients. A second randomization, to rituximab maintenance or interferon, showed that the extended administration of rituximab prolonged the time to lymphoma progression by more than two years on average.
Although maintenance rituximab has been shown to prolong remissions in patients with follicular lymphoma after rituximab plus chemotherapy, this is the first time that rituximab has been shown to have a similar effect in mantle cell lymphoma, a type of lymphoma in which remissions tend to be shorter and more difficult to treat.