Characteristics and predictors associated with cancer-related fatigue among solid and liquid tumors.

PURPOSE: Cancer-related fatigue (CRF) is a devastating complication with limited recognized clinical risk factors. We examined characteristics among solid and liquid cancers utilizing Machine learning (ML) approaches for predicting CRF. METHODS: We utilized 2017 National Inpatient Sample database and employed generalized linear models to assess the association between CRF and the outcome of burden of illness among hospitalized solid and non-solid tumors patients. And further applied lasso, ridge and Random Forest (RF) for building our linear and non-linear ML models. RESULTS: The 2017 database included 196,330 prostate (PCa), 66,385 leukemia (Leuk), 107,245 multiple myeloma (MM), and 41,185 cancers of lip, oral cavity and pharynx (CLOP) patients, and among them, there were 225, 140, 125 and 115 CRF patients, respectively. CRF was associated with a higher burden of illness among Leuk and MM, and higher mortality among PCa. For the PCa patients, both the test and the training data had best areas under the ROC curve [AUC = 0.91 (test) vs. 0.90 (train)] for both lasso and ridge ML. For the CLOP, this was 0.86 and 0.79 for ridge; 0.87 and 0.84 for lasso; 0.82 for both test and train for RF and for the Leuk cohort, 0.81 (test) and 0.76 (train) for both ridge and lasso. CONCLUSION: This study provided an effective platform to assess potential risks and outcomes of CRF in patients hospitalized for the management of solid and non-solid tumors. Our study showed ML methods performed well in predicting the CRF among solid and liquid tumors.

Bortezomib advanced mechanisms of action in multiple myeloma, solid and liquid tumors along with its novel therapeutic applications.

Bortezomib (BTZ) is a first-in-class reversible and selective proteasome inhibitor. It inhibits the ubiquitin proteasome pathway that leads to the degradation of many intracellular proteins. Initially, BTZ was FDA approved for the treatment of refractory or relapsed multiple myeloma (MM) in 2003. Later, its usage was approved for patients with previously untreated MM. In 2006, BTZ was approved for the treatment of relapsed or refractory Mantle Cell Lymphoma (MCL) and, in 2014, for previously untreated MCL. BTZ has been extensively studied either alone or in combination with other drugs for the treatment of different liquid tumors especially in MM. However, limited data evaluated the efficacy and safety of using BTZ in patients with solid tumors. In this review, we will discuss the advanced and novel mechanisms of action of BTZ documented in MM, solid tumors and liquid tumors. Moreover, we will shed the light on the newly discovered pharmacological effects of BTZ in other prevalent diseases.

Remission of liquid tumors and SARS-CoV-2 infection: A literature review.

The coronavirus disease 2019 (COVID-19) pandemic has produced a new global challenge for patients with cancer. The disease and the immunosuppression induced by cancer therapies have generated a perfect storm of conditions to increase the severity of the symptoms and worsen the prognosis. However, a few clinical reports showcased the power of viruses to induce remission in some patients suffering from liquid tumors. Here, we reviewed six cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that resulted in cancer remission, simultaneously highlighting the strengths and the unique challenges of oncolytic virotherapy. Virotherapy has become a special case of cancer immunotherapy. This paradigm-shifting concept suggests that oncolytic viruses are not only promising agents to combat particularly immunologically suppressed, immunotherapy-resistant tumors but also that the trigger of local inflammation, such as SARS-CoV-2 infection of the respiratory pathways, may trigger an abscopal effect sufficient to induce the remission of systemic cancer.

The impact of molecular tumor profiling on the design strategies for targeting myeloid leukemia and EGFR/CD44-positive solid tumors.

Nanomedicine has emerged as a novel cancer treatment and diagnostic modality, whose design constantly evolves towards increasing the safety and efficacy of the chemotherapeutic and diagnostic protocols. Molecular diagnostics, which create a great amount of data related to the unique molecular signatures of each tumor subtype, have emerged as an important tool for detailed profiling of tumors. They provide an opportunity to develop targeting agents for early detection and diagnosis, and to select the most effective combinatorial treatment options. Alongside, the design of the nanoscale carriers needs to cope with novel trends of molecular screening. Also, multiple targeting ligands needed for robust and specific interactions with the targeted cell populations have to be introduced, which should result in substantial improvements in safety and efficacy of the cancer treatment. This article will focus on novel design strategies for nanoscale drug delivery systems, based on the unique molecular signatures of myeloid leukemia and EGFR/CD44-positive solid tumors, and the impact of novel discoveries in molecular tumor profiles on future chemotherapeutic protocols.

Double attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab-mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activity.

BACKGROUND: Tumor-targeted nanoparticles hold great promise as new tools for therapy of liquid cancers. Furthermore, the therapeutic efficacy of nanoparticles can be improved by enhancing the cancer cellular internalization. METHODS: In this study, we developed a humanized bispecific antibody (BsAbs: CD20 Ab-mPEG scFv) which retains the clinical anti-CD20 whole antibody (Ofatumumab) and is fused with an anti-mPEG single chain antibody (scFv) that can target the systemic liquid tumor cells. This combination achieves the therapeutic function and simultaneously "grabs" Lipo-Dox® (PEGylated liposomal doxorubicin, PLD) to enhance the cellular internalization and anticancer activity of PLD. RESULTS: We successfully constructed the CD20 Ab-mPEG scFv and proved that CD20 Ab-mPEG scFv can target CD20-expressing Raji cells and simultaneously grab PEGylated liposomal DiD increasing the internalization ability up to 60% in 24 h. We further showed that the combination of CD20 Ab-mPEG scFv and PLD successfully led to a ninefold increase in tumor cytotoxicity (LC50: 0.38 nM) compared to the CD20 Ab-DNS scFv and PLD (lC50: 3.45 nM) in vitro. Importantly, a combination of CD20 Ab-mPEG scFv and PLD had greater anti-liquid tumor efficacy (P = 0.0005) in Raji-bearing mice than CD20 Ab-DNS scFv and PLD. CONCLUSION: Our results indicate that this "double-attack" strategy using CD20 Ab-mPEG scFv and PLD can retain the tumor targeting (first attack) and confer PLD tumor-selectivity (second attack) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.