Network - Winter 2013
Protein feeds brain tumors’ sugar habit, new drug acts to block it
A protein that sneaks into the cell nucleus and sets off two separate cancer-promoting processes vital to the development of malignant brain tumors makes itself an enticing target for therapy.
Having exposed that dangerous behavior by pyruvate kinase M2 (PKM2) in a series of major publications, MD Anderson researcher Zhimin Lu, M.D., Ph.D., has uncovered a vulnerability he thinks could turn the metabolic protein into “an Achilles’ heel for cancer.”
In a recent paper in Nature Cell Biology, Lu and colleagues identified a drug that inhibits the growth of brain tumors in mice by thwarting PKM2.
Lu, an associate professor in the Department of Neuro-Oncology, and colleagues have discovered:
- the cellular mechanism that overexpresses PKM2 in cancer cells;
- the complex pathway that smuggles PKM2 into the cell nucleus; and
- how, in the nucleus, PKM2 activates genes involved in cell division and in a glucose metabolism pathway that nourishes brain tumors and other types of cancer called the Warburg effect.
“For tumors to form, PKM2 must get to the nucleus to activate genes involved in cell proliferation and the Warburg effect,” Lu said. “If we can keep it out of the nucleus, we can block both of those cancer-promoting pathways.”
Cancer stem cells found among low-PSA cells
Prostate cancer cells that defy treatment and display heightened tumor-generating capacity can be identified by levels of prostate specific antigen (PSA) expressed in the tumor cells. Using a new technique, researchers were able, for the first time, to separate low-PSA and high-PSA prostate cancer cells, leading to a discovery that the low-PSA population of cancer stem cells appears to be an important source of castration-resistant prostate cancer.
Low-PSA cells were found to be both self-renewing and capable of differentiating into other prostate cancer cell types upon division. The findings demonstrate the need to develop new therapeutics that will target low-PSA prostate cancer cells that can be combined with hormone therapy to wipe out cancer cells and prevent recurrence.
The study’s senior author is Dean Tang, Ph.D., professor in the Department of Molecular Carcinogenesis.
New options for treatment-resistant chronic myeloid leukemia and one type of acute lymphoblastic leukemia
Patients with chronic myeloid leukemia (CML) or acute lymphoblastic leukemia that carries the Philadelphia chromosome who can’t tolerate the targeted drugs that revolutionized care for these leukemias now have three new options.
The U.S. Food and Drug Administration has approved ponatinib (Iclusig), an effective drug for many patients with treatment-resistant disease. It joins bosutinib (Bosulif) and
omacetaxine (Synribo), also recently approved.
These drugs may be effective for the 30% to 40% of CML patients whose disease is resistant to imatinib (Gleevec). Second-generation drugs nilotinib (Tasigna) and dasatinib
(Sprycel) are effective for about half of those patients.
The three new drugs work by thwarting treatment-resistant mutations (Ponatinib and bosutinib) or by stifling creation of an aberrant protein (omacetaxine).
“It’s important to have as many therapies against cancer as we can, because rarely does one drug or combination succeed for all patients,” said Jorge Cortes, M.D., professor in the Department of Leukemia, who led all clinical trials for the three new drugs.
In this issue
Head and neck cancer survivor stays positive
Doctor, Doctor: Focus on sepsis
‘A clinical instinct:’ Hospitalists improve care for acutely ill inpatients
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