Cancer management during the COVID-19 world pandemic.

Since 2019, the world has been experiencing an outbreak of a novel beta-coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV)-2. The worldwide spread of this virus has been a severe challenge for public health, and the World Health Organization declared the outbreak a public health emergency of international concern. As of June 8, 2023, the virus' rapid spread had caused over 767 million infections and more than 6.94 million deaths worldwide. Unlike previous SARS-CoV-1 and Middle East respiratory syndrome coronavirus outbreaks, the COVID-19 outbreak has led to a high death rate in infected patients; this has been caused by multiorgan failure, which might be due to the widespread presence of angiotensin-converting enzyme 2 (ACE2) receptors-functional receptors of SARS-CoV-2-in multiple organs. Patients with cancer may be particularly susceptible to COVID-19 because cancer treatments (e.g., chemotherapy, immunotherapy) suppress the immune system. Thus, patients with cancer and COVID-19 may have a poor prognosis. Knowing how to manage the treatment of patients with cancer who may be infected with SARS-CoV-2 is essential. Treatment decisions must be made on a case-by-case basis, and patient stratification is necessary during COVID-19 outbreaks. Here, we review the management of COVID-19 in patients with cancer and focus on the measures that should be adopted for these patients on the basis of the organs or tissues affected by cancer and by the tumor stage.

Therapeutic cancer vaccines: From biological mechanisms and engineering to ongoing clinical trials.

Therapeutic vaccines are currently at the forefront of medical innovation. Various endeavors have been made to develop more consolidated approaches to producing nucleic acid-based vaccines, both DNA and mRNA vaccines. These innovations have continued to propel therapeutic platforms forward, especially for mRNA vaccines, after the successes that drove emergency FDA approval of two mRNA vaccines against SARS-CoV-2. These vaccines use modified mRNAs and lipid nanoparticles to improve stability, antigen translation, and delivery by evading innate immune activation. Simple alterations of mRNA structure- such as non-replicating, modified, or self-amplifying mRNAs- can provide flexibility for future vaccine development. For protein vaccines, the use of long synthetic peptides of tumor antigens instead of short peptides has further enhanced antigen delivery success and peptide stability. Efforts to identify and target neoantigens instead of antigens shared between tumor cells and normal cells have also improved protein-based vaccines. Other approaches use inactivated patient-derived tumor cells to elicit immune responses, or purified tumor antigens are given to patient-derived dendritic cells that are activated in vitro prior to reinjection. This review will discuss recent developments in therapeutic cancer vaccines such as, mode of action and engineering new types of anticancer vaccines, in order to summarize the latest preclinical and clinical data for further discussion of ongoing clinical endeavors in the field.

Targeting Aberrant FGFR Signaling to Overcome CDK4/6 Inhibitor Resistance in Breast Cancer.

Breast cancer (BC) is the most common cause of cancer-related death in women worldwide. Therapies targeting molecular pathways altered in BC had significantly enhanced treatment options for BC over the last decades, which ultimately improved the lives of millions of women worldwide. Among various molecular pathways accruing substantial interest for the development of targeted therapies are cyclin-dependent kinases (CDKs)-in particular, the two closely related members CDK4 and CDK6. CDK4/6 inhibitors indirectly trigger the dephosphorylation of retinoblastoma tumor suppressor protein by blocking CDK4/6, thereby blocking the cell cycle transition from the G1 to S phase. Although the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib gained FDA approval for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC as they significantly improved progression-free survival (PFS) in randomized clinical trials, regrettably, some patients showed resistance to these therapies. Though multiple molecular pathways could be mechanistically responsible for CDK4/6 inhibitor therapy resistance, one of the most predominant ones seems to be the fibroblast growth factor receptor (FGFR) pathway. FGFRs are involved in many aspects of cancer formation, such as cell proliferation, differentiation, and growth. Importantly, FGFRs are frequently mutated in BC, and their overexpression and/or hyperactivation correlates with CDK4/6 inhibitor resistance and shortened PFS in BC. Intriguingly, the inhibition of aberrant FGFR activity is capable of reversing the resistance to CDK4/6 inhibitors. This review summarizes the molecular background of FGFR signaling and discusses the role of aberrant FGFR signaling during cancer development in general and during the development of CDK4/6 inhibitor resistance in BC in particular, together with other possible mechanisms for resistance to CDK4/6 inhibitors. Subsequently, future directions on novel therapeutic strategies targeting FGFR signaling to overcome such resistance during BC treatment will be further debated.

Current margin practice and effect on re-excision rates following the publication of the SSO-ASTRO consensus and ABS consensus guidelines: a national prospective study of 2858 women undergoing breast-conserving therapy in the UK and Ireland.

INTRODUCTION: There is variation in margin policy for breast conserving therapy (BCT) in the UK and Ireland. In response to the Society of Surgical Oncology and American Society for Radiation Oncology (SSO-ASTRO) margin consensus ('no ink on tumour' for invasive and 2 mm for ductal carcinoma in situ [DCIS]) and the Association of Breast Surgery (ABS) consensus (1 mm for invasive and DCIS), we report on current margin practice and unit infrastructure in the UK and Ireland and describe how these factors impact on re-excision rates. METHODS: A trainee collaborative-led multicentre prospective study was conducted in the UK and Ireland between 1st February and 31st May 2016. Data were collected on consecutive BCT patients and on local infrastructure and policies. RESULTS: A total of 79 sites participated in the data collection (75% screening units; average 372 cancers annually, range 70-900). For DCIS, 53.2% of units accept 1 mm and 38% accept 2-mm margins. For invasive disease 77.2% accept 1 mm and 13.9% accept 'no ink on tumour'. A total of 2858 patients underwent BCT with a mean re-excision rate of 17.2% across units (range 0-41%). The re-excision rate would be reduced to 15% if all units applied SSO-ASTRO guidelines and to 14.8% if all units followed ABS guidelines. Of those who required re-operation, 65% had disease present at margin. CONCLUSION: There continues to be large variation in margin policy and re-excision rates across units. Altering margin policies to follow either SSO-ASTRO or ABS guidelines would result in a modest reduction in the national re-excision rate. Most re-excisions are for involved margins rather than close margins.

Congestive heart failure: experimental model.

INTRODUCTION: Surgically induced, combined volume and pressure overload has been used in rabbits to create a simplified and reproducible model of acute left ventricular (LV) failure. MATERIALS AND METHODS: New Zealand white male rabbits (n = 24, mean weight 3.1 ± 0.2 kg) were randomly assigned to either the Control group (n = 10) or to the Heart Failure group (HF, n = 14). Animals in the Control group underwent "sham" procedures. Animals in the HF group underwent procedures to induce LV volume overload by inducing severe aortic valve regurgitation with aortic cusp disruption and pressure overload using an occlusive silver clip positioned around the pre-renal abdominal aorta. RESULTS: Following Procedure-1 (volume overload) echocardiography confirmed severe aortic regurgitation in all animals in the HF group, with increased mean pulse pressure difference from 18 ± 3 to 38 ± 3 mmHg (P < 0.0001). After Procedure-2 (pressure overload) all animals in the HF group showed clinical and echocardiographic signs of constriction of the abdominal aorta and echocardiography confirmed progressively declining LV function. At the end of the protocol there was a significant increase of the heart/body weight ratio in the HF group vs. Control group (4.6 ± 0.2 vs. 2.9 ± 0.1 g/kg, P < 0.05), and echocardiography showed in HF group significant increase of the LV end-diastolic diameter (2.15 ± 0.09 vs. 1.49 ± 0.03 cm, P < 0.001) and reduction of the LV shortening fraction (26.3 ± 3.8 vs. 41.3 ± 1.6%, P < 0.001). CONCLUSION: This experimental model: (a) consistently produces LV hypertrophy/dilatation and subsequent congestive heart failure, (b) provides new data on the time course of LV dilatation, hypertrophy and failure, (c) allows study of the progress and evolution of LV systolic and diastolic dysfunction in the presence of induced LV failure, (d) is suitable to study intervention or pharmacological administration to reduce the negative effects of acute LV failure.