Table 2.
Comparative oncology reveals widespread similarities in cancer development and pathology in between human and rhesus macaques
| Cancer in rhesus macaques | Ref | |
| Age | Similar increase in cancer incidence in aging/geriatric population. | 47 |
| Immune competence | Similar reports of declining immune competence and TCR repertoire with age, resembling the immune situation in aging patients with human cancer. | 6 52 53 |
| Viral infections | Rhesus rhadinovirus in SIV-infected rhesus macaques is similarly associated with mesenchymal malignancies as Kaposi’s sarcoma-associated herpesvirus in HIV-infected humans. | 56 57 |
| Epstein-Barr virus homologue rhesus lymphocryptovirus is associated with B-cell lymphomas and hairy leukoplakia in SIV-infected macaques. | 58 | |
| Papilloma virus is present in wild rhesus macaques (88/117) and is sexually transmitted in breeding colonies. | 63–65 | |
| HPV analog RhPV-1 is associated with penile carcinoma, dysplastic lesions, acetowhitening (35%), and two cervical carcinomas in a breeding colony (n=31, transmission rate 71%). | 63 | |
| Inherited mutations | Rhesus equivalent of HNPCC/Lynch syndrome is linked to germline MLH1 promoter deletion, de novo stop codon in MLH1, and deleterious missense mutations in MSH6. | 67 68 |
| No description of BRCA1/2 involvement in NHP yet, potentially due to the limited germline/phenotype information. | ||
| Colorectal cancer | ||
| Prevalence | Neoplasia of the gastrointestinal system is the most commonly diagnosed in rhesus macaques with adenocarcinoma of the large intestines as most prevalent tumor. | 47 |
| Symptoms | Similar clinical signs as in humans including weight loss, intermittent diarrhea, hypoproteinemia, fecal occult blood, and microcytic anemia. | 47 75 77 78 |
| Location | Humans: Throughout the ascending/transverse/descending/sigmoid colon and rectum. Rhesus macaques: Mostly right-sided (ileocecal junction, ascending colon). |
|
| Precancerous lesions | Humans: Colonic polyps are well established as precancerous lesions. Rhesus macaques: Polyps are not reported and CRC usually infiltrates within colonic wall. |
79 |
| Progression and metastatic spread | Humans: Metastatic spread is common in late stages and a major factor for CRC mortality, frequently to liver and other distant organs such as lung. Rhesus macaques: Constriction of the colonic lumen by the primary lesion and blocking passage is the major cause for a humane endpoint in rhesus macaques, treatment resistant anemia (iron/B12 supplement) can be frequently observed, local lymph node metastasis, distant metastatic spread (eg, bone/spine), and abdominal carcinomatosis (eg, omentum, uterus, stomach, pancreas) is observed in certain cases. |
86 |
| Mismatch repair deficiency | MMRd in rhesus CRCs results in microsatellite instability as reported in human CRCs. | 67 68 |
| Breast cancer | ||
| Lifetime incidence | Six per cent in female macaques compared with 13% in American women (note: under-reporting and difference in risk factor exposure in macaques). |
76 92 93 |
| Histology | Similar mammary gland anatomy, development patterns, regression, and sex steroid receptor expression. | 94 |
| Sex hormones | Similar patterns of estrogen, progesterone, luteinizing hormone, and follicle stimulation hormone in human, cynomolgus, and rhesus macaques. | 95 |
| Histopathology | Similar range of atypical hyperplasia, DCIS, and invasive ductal carcinomas reported. | 76 |
| Progression and metastatic spread | Similar progression and metastatic spread to axillary lymph nodes, lung, and chest wall can be observed in rhesus macaques and humans. | 47 76 |
| Receptor expression in BC | Subtypes described in humans are similarly observed in rhesus macaques incl. Luminal A (HR+/HER2–), HER2 (HR–/HER2+), and triple-negative BC (HR–/HER2–). | 76 94 |
BC, breast cancer; CRC, colorectal cancer; DCIS, ductal carcinoma in situ; HER2, human epidermal growth factor receptor 2; HNPCC, hereditary non-polyposis colorectal cancer; HPV, human papilloma virus; NHP, non-human primates; RhPV, rhesus specific papillomavirus; SIV, simian immunodeficiency virus; TCR, T cell receptor.