Prostate cancer risk in men of differing genetic ancestry and approaches to disease screening and management in these groupsMcHugh, Jana; Saunders, Edward J.; Dadaev, Tokhir; McGrowder, Eva; Bancroft, Elizabeth; Kote-Jarai, Zsofia; Eeles, Rosalind
doi: 10.1038/s41416-021-01669-3pmid: 34923574
Prostate cancer is the second most common solid tumour in men worldwide and it is also the most common cancer affecting men of African descent. Prostate cancer incidence and mortality vary across regions and populations. Some of this is explained by a large heritable component of this disease. It has been established that men of African and African Caribbean ethnicity are predisposed to prostate cancer (PrCa) that can have an earlier onset and a more aggressive course, thereby leading to poorer outcomes for patients in this group. Literature searches were carried out using the PubMed, EMBASE and Cochrane Library databases to identify studies associated with PrCa risk and its association with ancestry, screening and management of PrCa. In order to be included, studies were required to be published in English in full-text form. An attractive approach is to identify high-risk groups and develop a targeted screening programme for them as the benefits of population-wide screening in PrCa using prostate-specific antigen (PSA) testing in general population screening have shown evidence of benefit; however, the harms are considered to weigh heavier because screening using PSA testing can lead to over-diagnosis and over-treatment. The aim of targeted screening of higher-risk groups identified by genetic risk stratification is to reduce over-diagnosis and treat those who are most likely to benefit.
Incidence trends for twelve cancers in younger adults—a rapid reviewdi Martino, Erica; Smith, Lesley; Bradley, Stephen H.; Hemphill, Scott; Wright, Judy; Renzi, Cristina; Bergin, Rebecca; Emery, Jon; Neal, Richard D.
doi: 10.1038/s41416-022-01704-xpmid: 35132237
Many cancer referral guidelines use patient’s age as a key criterium to decide who should be referred urgently. A recent rise in the incidence of colorectal cancer in younger adults has been described in high-income countries worldwide. Information on other cancers is more limited. The aim of this rapid review was to determine whether other cancers are also increasing in younger age groups, as this may have important implications for prioritising patients for investigation and referral. We searched MEDLINE, Embase and Web of Science for studies describing age-related incidence trends for colorectal, bladder, lung, oesophagus, pancreas, stomach, breast, ovarian, uterine, kidney and laryngeal cancer and myeloma. ‘Younger’ patients were defined based on NICE guidelines for cancer referral. Ninety-eight studies met the inclusion criteria. Findings show that the incidence of colorectal, breast, kidney, pancreas, uterine cancer is increasing in younger age groups, whilst the incidence of lung, laryngeal and bladder cancer is decreasing. Data for oesophageal, stomach, ovarian cancer and myeloma were inconclusive. Overall, this review provides evidence that some cancers are increasingly being diagnosed in younger age groups, although the mechanisms remain unclear. Cancer investigation and referral guidelines may need updating in light of these trends.
Increased expression of Profilin potentiates chemotherapeutic agent-mediated tumour regressionSaurav, Shashank; Manna, Sunil Kumar
doi: 10.1038/s41416-021-01683-5pmid: 35022526
BackgroundTargeted cancer therapy is an alternative to standard chemotherapy for a better prognosis. Although its incompetency for triple-negative breast cancer (TNBC), treatment still relies on classical chemotherapy. Increasing evidence suggest that chemotherapeutic drug-induced toxic effect could be minimised by combinatorial therapy. Profilin’s familiar anti-tumorigenic activity can be utilised in combination with the drug to improve efficacy, which could be promising therapeutics to treat TNBC.MethodsAll-trans retinoic acid (ATRA) in combination with vinblastine was tested on human MDA MB-231 cell line (MB-231) (in vitro) and MB-231 borne breast cancer in nude mice (in vivo). Effects of combination treatment on tumour growth inhibition and apoptosis were examined by tumour volume, histology and PARP cleavage. ATRA-induced transcriptional regulation of profilin had been evaluated by gel-shift and reporter gene assays. Profilin’s role in ATRA-induced vinblastine efficacy was validated in profilin-stable and profilin-silenced cells.ResultsATRA binds with RAR/RXR to increase the profilin expression that potentiated cell death by chemotherapeutics. ATRA priming led to vinblastine-mediated potentiation of G2–M phase cell cycle arrest in MB-231 cells and regression of breast cancer in xenograft mice at very low concentration without any adverse effects. Moreover, increased p53 and PTEN but downregulated p65 in the tumour tissues further supported the involvement of profilin for tumour regression.ConclusionsVinblastine at very low concentration (20 times lesser than the recommended dose for breast cancer therapeutic) significantly regress tumour growth in ATRA-primed mice without any toxic effects suggesting potential combinatorial therapeutics for TNBC.