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Recent Submissions

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Future directions in cervical cancer treatment
(Academic Press (Strategies for Overcoming Chemotherapy Resistance in Cervical Cancer), 2024-02) Damane, Botle Precious; Mulaudzi, Thanyani Victor; Kgokolo, Cordelia Mahlatse; Luvhengo, Thifhelimbilu; Skepu, Amanda; Rotim, Solomon O.; Dlamini, Zodwa
Immunotherapy has been a breakthrough in the treatment of several cancers with limited adverse effects compared to other therapies. Patients have experienced remission with undetectable cancers for an impressive number of years. However, the success rate is only observed in about 15%–20% of cases indicating that there is still a tremendous need for targeted therapies that are efficient in all cancers with limited or no adverse effects. The combination of immunotherapy with the existing chemotherapeutic regimens has shown improvement in several other cancers, but resistance is still a hindering factor. Thus, the application of nanomedicine, computational oncology, artificial intelligence (AI), and molecularly targeted therapies with the consideration of indigenous knowledge are reshaping the future development of cancer therapies. Together, these oncotherapeutic modalities could reshape cancer-preventative strategies, improve precision oncology, and decipher drug resistance. They offer the ability to deliver specific drugs/compounds to a specific location and ensure their efficaciousness whilst protecting the surrounding tissue. This effect takes place even in events where multiple therapeutic approaches are employed. Thus, the future of cancer therapies particularly that of the most common cancers such as cervical cancer is promising. Continual improvement of the golden standards of therapy such as radiotherapy with technologies that can detect and treat cancer simultaneously can potentially improve patient care and clinical outcomes.
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Exploring the State of Cancer Imaging Research in Africa
(Journal of the American College of Radiology Volume 21, Issue 8,, 2024-08) Olawole, Tolulope; Oyetunde, Tolulope; Uzomah, Uche; Shanahan, Justin; Hartmann, Katherine; Rotimi, Solomon; Dako, Farouk
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Advancements in Biomarkers of Prostate Cancer: A Review
(2024) Agbetuyi-Tayo, Praise; Gbadebo, Mary; Rotimi, OluwakemiA.; Rotim, Solomon O
Prostate cancer (PCa) is one of the most prevalent and deadly cancers among men, particularly affecting men of African descent and contributing significantly to cancer-related morbidity and mortality worldwide. The disease varies widely, from slow-devel oping forms to highly aggressive or potentially fatal variants. Accurate risk stratification is crucial for making therapeutic decisions and designing adequate clinical trials. This review assesses a broad spectrum of diagnostic and prognostic biomarkers, many of which are incorporated into clinical guidelines, including the Prostate Health Index (PHI), 4Kscore, STHLM3, PCA3, SelectMDx, ExoDx Prostate Intelliscore (EPI), and MiPS. It also highlights emerging biomarkers with preclinical support, such as urinary non-coding RNAs and DNA methylation patterns. Additionally, the review explores the role of tumor-associated microbiota in PCa, offering new insights into its potential contributions to disease understanding. By examining the latest advance ments in PCa biomarkers, this review enhances understanding their roles in disease management.
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Abstract 4343: Revealing ovarian cancer copy number variation in single cells
(American Association for Cancer Research Cancer Res (2024) 84 (6_Supplement): 4343, 2024-03-15) Jin, Yuxin; Bassiouni, Rania; Rania, Lee D.; Qian, Jing; Rotimi, Solomon; Webb, Michelle G.; Rajpara, Seeta; Craig, David W.; Roman, Lynda D.; Carpten, John D.
The mortality rate associated with ovarian cancer (OvCa) is disproportionately high in comparison to its incidence rate. This is partly due to the heterogeneous nature of the disease, which reduces treatment efficacy and contributes to high rates of relapse and chemotherapy resistance. Most OvCa are epithelial in origin and can be classified into four main subtypes: serous, mucinous, endometrioid, and clear cell. Of these, high grade serous ovarian cancer (HGSOC) is the deadliest. Epithelial ovarian carcinomas (EOC) typically exhibit widespread chromosomal and arm-level copy number abnormalities across most of the genome; in HGSOC, focal amplifications and microdeletions are especially prevalent and indicative of high genomic instability. To understand the heterogeneity of aneuploidy in EOC and HGSOC, we performe single-cell whole genome sequencing on four EOC samples: two HGSOC, one clear cell, and one mixed clear cell and endometrioid. All samples were late stage and treatment naïve, and one sample had a known BRCA2 mutation. Sequencing data was processed by two complementary methods to call copy number alterations. First, we used the Cell Ranger DNA pipeline (10x Genomics) to align cell-identified sequencing reads to human reference genome GRCh38 for coverage-based copy number estimation. Resulting copy number calls were cleaned up for mappability, quality, and noisiness. Each sample was then subject to clustering and subclustering analysis using maximum likelihood genetic clustering algorithms. All samples exhibited a high level of aneuploidy, including characteristic alterations known to be associated with EOC. Two tumors contained readily distinguishable clonal populations, and all samples contained main tumor clones that could be further divided by unique subclonal characteristics. Evidence of polyploidy was also seen in all four specimens, with some tumor clusters exhibiting triploid and tetraploid baselines. In parallel, sequencing data was analyzed by the Copy-number Haplotype Inference in Single-cell by Evolutionary Links (CHISEL) algorithm. CHISEL utilizes both binned read depth ratio and B-allele frequency data to determine allele- and haplotype-specific copy numbers in single cells. Results from CHISEL confirmed the copy number calls from Cell Ranger DNA, and revealed widespread loss of heterozygosity in all samples. These findings were corroborated with allele-specific copy number data derived from matched tumor-normal whole exome sequencing. Furthermore, CHISEL detected polyploidy in one-third of the tumor cells with no preference for the A or B alleles. Overall, our findings highlight that the known heterogeneity of ovarian cancer extends to the level of aneuploidy and CNAs, shedding light on factors which pose significant barriers to effective personalized medicine implementation.
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Abstract 3455: Prevalence of monoclonal gammopathy of undetermined significance (MGUS) in a Western Nigerian population
(Volume 84, Issue 6_Supplement POSTER PRESENTATIONS - PROFFERED ABSTRACTS, 2024-03-15) Vachon, Celine M; Allmer, Cristine; Moonen, Danelle; Norman, Aaron; Cook, Joselle; Slager, Susan; Rotimi, Oluwakemi A.; De Campos, Opeyemi C; Dokumu, Titilope M.; Murray, David; Kumar, Shaji; Brown, Elizabeth; Baughnm, Linda B; Rotimi, Solomon
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition characterized by plasma cell production of monoclonal (M) protein and is a requisite precursor to multiple myeloma (MM). African American (AA) individuals have a two-fold higher incidence of MGUS and MM compared to White individuals. However, data are limited on individuals from Africa, especially using sensitive MGUS detection methods. We examined the prevalence of MGUS in a sample of the general population in Nigeria. Individuals aged 40 and over (n=343) were recruited through health promotion events in Ado-Odo Ota Local Government Area of Ogun State, Nigeria, and provided informed consent, a blood sample, and a short questionnaire. Serum was screened at Mayo Clinic for heavy chain (HC)-MGUS using the matrix-assisted laser desorption/ionization-time of flight (Mass-Fix) assay, which has high sensitivity for detection of M-proteins; serum free light chains (FLC) were also measured. FLC was abnormal if the kappa (>0.26 mg/dL) or lambda (>0.33 mg/dL) light chain (LC) was elevated and FLC ratio (kappa/lambda) was outside the reference range (0.26-3.10). LC-MGUS was defined as an abnormal FLC in the absence of a HC. Age- and sex adjusted prevalence rates were directly standardized to 2010 United States (US) population for comparison to published studies. Logistic regression was used to examine the association of age, sex, and BMI with HC-MGUS. The mean age of participants was 55 years (SD=10.9), and 74.6% were female. Of these, 216 (63%) had both parents from the Yoruba tribe, 89 (26%) from the Igbo tribe and 38 (11%) from other tribes. Overall, 33 participants (9.6%) had HC-MGUS, with 8 (2.3%) having an M protein above 0.2 g/dL; 6 (1.7%) had LC-MGUS. HC-MGUS was predominantly IgG isotype (48.5%), followed by IgA (27.3%), biclonal (15.2%) and IgM (9.0%). Prevalence of HC-MGUS was 8.3% for ages 40-49, 7.7% ages 50-69 and 22% ages 70 and above. Standardized to the US population, age and sex adjusted MGUS prevalence ages 50 and older was 17.3% (95% CI: 9.8%-24.9%) and HC-MGUS was 14.7% (95% CI: 7.7% 21.8%), similar to previously published rates of HC-MGUS using Mass-Fix screening of AA individuals (16.5%, 95% CI: 12.2%-20.8%) (PMID: 35316833). In models that included age, sex and BMI, older age was positively associated with HC-MGUS (OR=3.1, 95% CI: 1.1-8.7 for ages 70+ compared to <50), while female sex (OR=0.53, 95% CI: 0.24-1.2) and overweight/obesity (OR=0.34, 95% CI: 0.16-0.75 for BMI > 25 vs. <25) were inversely associated with HC-MGUS. We observed similar prevalence of HC MGUS at ages 50 and above among Western Nigerian and AA populations when screened using mass-spectrometry. Older age was positively associated with HC MGUS while overweight and obesity were inversely associated. Studies of MGUS in indigenous African populations may provide insight to unique cancer risk factors compared to other populations.