Current Challenges in Glioblastoma: Intratumour Heterogeneity, Residual Disease, and Models to Predict Disease Recurrence

Abstract

Glioblastoma (GB) is the most common primary malignant brain tumor, and despite the availability of chemotherapy and radiotherapy to combat the disease, overall survival remains low with a high incidence of tumor recurrence. Technological advances are continually improving our understanding of the disease, and in particular, our knowledge of clonal evolution, intratumor heterogeneity, and possible reservoirs of residual disease. These may inform how we approach clinical treatment and recurrence in GB. Mathematical modeling (including neural networks) and strategies such as multiple sampling during tumor resection and genetic analysis of circulating cancer cells, may be of great future benefit to help predict the nature of residual disease and resistance to standard and molecular therapies in GB.

5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells

“…For example, one type of cancer with such intrinsic resistance to apoptosis induction is glioblastoma multiforme (GBM). GBM cells are generally highly resistant to many different apoptotic stimuli resulting in low effectiveness of classical pro-apoptotic therapeutic approaches [3,4]. Indeed, GBM is characterized by a deregulated tumor genome containing opportunistic deletions of tumor suppressor genes as well as amplification or mutational hyper-activation of receptor tyrosine kinase receptors [5].…”

Silencing LDHA inhibits proliferation, induces apoptosis and increases chemosensitivity to temozolomide in glioma cells

“…Glioblastoma multiforme (GBM) is the most common and malignant brain tumor and has a median survival rate of less than two years (1,2). Current therapies, including surgery, radiotherapy and chemotherapy, are generally ineffective at controlling the progression and development of GBM, and recurrence is practically inevitable (3).…”

Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression

“…Increasing evidence suggests that the genetic, epigenetic, and signaling heterogeneity of GBM underlies the ineffectiveness of currently available therapeutics (1,2). Additionally, therapeutic schemes devised to challenge brain tumor cells are frequently thwarted by insufficient delivery caused by pharmacokinetics, the blood-brain barrier (BBB), and an altered tumor microenvironment in which tumor-derived signaling recruits immunomodulatory cells and induces extracellular matrix remodeling to build safe harbors of tumorigenic niches (3)(4)(5). These obstacles call for tailored therapeutic strategies to counter tumor heterogeneity and overcome roadblocks in delivery.…”