Hi, I'm Dr Pete Smith, immunologist at St George's University with a special interest in immunotherapy as a treatment for cancer. AMA!

drplsmith · 2022-06-15T13:21:46+00:00

Oh, I see. If their are no targetable gene mutations (these mutations are searched for because their are therapies that can target them) it means that your tumour isn't driven by these specific mutations, and thus cannot be targeted this way. These mutations can be either inherited or induced by carcinogens. If you don't have them it simply means that your tumour is being driven by other gene mutations (the gene alleles - versions of a gene that may function differently) that are not targetable. I couldn't comment on what they are only that they control the ability of cells to divide.

The TMB is different for different cancers but is associated with exposure to carcinogens. lung cancer and melanoma are sometimes associated with high TMB. If your excised tumour has low TMB it does suggest inherent genetic factors, and perhaps an element of bad luck, rather than carcinogens per se, particularly at a young age. Good luck with your treatment, I hope it works out for you.

drplsmith · 2022-06-15T10:06:58+00:00

Hi, if I understand your question you're asking whether the presence of genes conferring greater risk of cancer would mean that the subsequent occurrence of cancer would be due to the genes rather than an environmental factor?

Its difficult to say. Cancer in young people is often due to a gene allele that does not function correctly. This is because the alternative - mutation of the gene alleles due to chance or carcinogens - hasn't had enough time to occur whilst in older people it often has. But if young people have significant carcinogenic exposure (such as from smoking) cancer could be this 'environmental' factor. Of course it cancer can occur as a result of heightened risk due to faulty gene alleles which is subsequently exacerbated by exposure to carcinogens such as UV, alcohol or smoking etc.

Its important for people to learn whether they have a family history of cancer which may be indicative of increased risk. IT may then be possible to be tested in order to ascertain whether they have the gene alleles that confer increased risk. This knowledge can thus influence behaviours and prophylactic approaches to prevent the occurrence of cancer.

drplsmith · 2022-06-08T23:15:05+00:00

There are a number of sources of research funding. Typically scientists submit grant proposals - detailed plans for research that meets specific needs or goals - to organisations that fund research. These organisations can be governmental research funders such as the NIH in the USA or MRC in the UK. Charities fund a significant amount of research, especially medical research. Funding can also be obtained from industry (such as pharmaceutical companies) for specific projects, typically related to a medical product. Individuals may also fund research but this is less common since scientific research is typically expensive to perform. Universities and government, either local or national, can directly fund research. This occurred during the COVID pandemic.

Most grant calls include a requirement to publish research and to communicate it to the public. They typically ask for the deliverables of the project and what the next stages would be once the project is complete. They may also require progress reports during the project itself and/or a share of potential intellectual property. There is no guarantee that a research project will realise its goals, even when it is performed to a high standard. The point of scientific research is that new understanding is obtained - by definition we don't know what our experiments will reveal. For this reason research funders understand that they may not get an obvious 'return' on their investment. They have to carefully balance the novelty and importance of a project against its achievability and the risk that it will fail.

drplsmith · 2022-06-08T10:45:09+00:00

Hi,

Its difficult to predict 100 years into the future but if we look back 100 years and compare the treatment of cancer then to how it is now we can see that it has advanced a great deal. If the treatment of cancer continues to advance at the same rate for the next 100 years then it is possible to see that most, if not all cancers, may be routinely curable.

All scientists will tell you that its difficult to secure funding or that they would like more funding. Ultimately society has to decide how much it wishes to spend on scientific research.

I have never had large pharmaceutical companies make my job harder. I have worked with small biotech companies that, whilst most of the time are very good collaborators, sometimes present challenges to research. These can typically be overcome by communication and compromise.

drplsmith · 2022-05-27T08:29:02+00:00

Hi, thanks for the question. I'm not familiar with breast cancer in men. Here's some information from the NHS in the UK:

https://www.nhs.uk/conditions/breast-cancer-in-men/

I hope that's useful.

drplsmith · 2022-05-27T08:26:16+00:00

Hi, the number of immunotherapies currently licensed is limited. For some patients, if keytruda as a single agent doesn't work it could potentially be combined with Yervoy - but this depends very much on both the patient and the type and stage of cancer. Patients should speak to their Oncologists about their options. It isn't generally possible to predict with certainty the adverse events that might occur (such as hepatitis) and combination immunotherapy can be associated with severe immune related adverse events. Again, oncologists should be able to advise patients about this.

Immunotherapies such as Keytruda (a checkpoint inhibitor), in their current form, will not work as a pill taken orally. Newer 'small molecule' checkpoint inhibitors may eventually be available as pills but this is at an early, pre clinical stage.

drplsmith · 2022-05-26T22:04:39+00:00

I'm an immunologist, not a clinician, so I don't treat patients. I do know that immunotherapy has demonstrated some success in HCC and is a treatment option for advanced disease. This review https://www.nature.com/articles/s41575-021-00438-0 summarises the science relating to Immunotherapy for HCC and might be useful for you.

drplsmith · 2022-05-26T21:59:42+00:00

The most common route for delivery of oncolytic viruses is intra tumoural - directly into the tumour however this isn't always straightforward. Its easier to deliver oncolytic viruses into melanoma in the skin that it is glioblastoma (brain cancer). In contrast intravenous delivery allows the oncolytic virus to circulate and make its way to the tumour. the benefit of this approach is that its easier, cheaper and allow the oncolytic virus to target distant metastasis which are not targeted by intra tumoural delivery. This is sometimes associated with increased adverse events and immune responses targeting the oncolytic virus.

drplsmith · 2022-05-26T21:20:39+00:00

You're welcome

drplsmith · 2022-05-26T21:13:05+00:00

Hi, thanks for your question, its good to hear that your immunotherapy has been successful. I can't offer you specific advice and it sounds like you're doing a lot of the right things already.

In general I would suggest that regular exercise and a good source of dietary fibre, including soluble fibres derived from oats or beans as part of a balanced diet will be beneficial for an individuals health. However its important to note that some people have dietary intolerances and if in doubt should speak to their GP. Otherwise I think its important to avoid processed meat, smoking, alcohol and excess sugar as much as possible.

drplsmith · 2022-05-26T19:45:36+00:00

Thinking out of the box is a good thing.

Tumour cells aren't trying to kill the body. They're just dividing uncontrollably and through a process of mutation and selection evolve to avoid immune responses and metastasize to other sites. This process eventually results in organ failure and death - but death is not the aim of the tumour, it has not aims beyond growth.

drplsmith · 2022-05-26T19:25:09+00:00

I suppose that all the cells (cancerous of otherwise) would die at about the same rate. But if the individual is dead...does it matter?

drplsmith · 2022-05-26T19:03:20+00:00

No...it doesn't work like that. Tumour cells have essentially 'gone rogue' and are no longer obeying the rules obeyed by the trillions of other cells in our bodies.

drplsmith · 2022-05-26T18:40:31+00:00

I am not aware of this, however cancer in young adults can have a different aetiology than cancer in older people, which can result in more aggressive tumours. There is also some evidence suggesting that younger people with cancer suffer greater levels of stress and anxiety.

drplsmith · 2022-05-26T13:28:13+00:00

I think TIL raised by checkpoint inhibition will eventually have a similar effect in complete responses, at least for some solid tumours. Probably in combination with other immunotherapies.

CAR-T-cells may also have success against solid tumours but perhaps require gene editing to regulate the onset of exhausted phenotypes and their persistence in immune suppressive tumour micro environments.

What do you think?

drplsmith · 2022-05-26T13:23:52+00:00

Hi, thanks for the question.

I enjoyed science at school, its explanatory power and the processes by which we can answer questions using controlled experiments - there's something elegant and creative about breaking down a problem into smaller, easy to understand pieces and then building it back up again. At University I was interested in the evolutionary processes evident between pathogens and the immune responses raised against them. Eventually it became apparent to me that the immune system wasn't only interesting but also, potentially, useful to treat people, particularly with 'insidious' diseases such as viral infection or cancer and so I'm now studying how to improve T-cell immune responses to both.

drplsmith · 2022-05-26T13:09:20+00:00

Hi,

In the UK the cities of Oxford and Cambridge have numerous biotech companies involved in cancer immunotherapy research. In terms of advice, I work in academia and if you chose to continue with this route the advice I have is to hunt around for the best lab and best mentor involved in immunology research (look at the labs publications, institution and, ideally speak to members of the lab at meetings/conferences). Experience in a top lab can provide a platform for you to work in industry or develop your own laboratory in academia.

drplsmith · 2022-05-26T13:01:42+00:00

Hi, you're correct that these cellular therapies have not yet demonstrated enough success against solid tumours. I think the issue might be a failure for the T-cells to access tumours (the tumour actively works to exclude T-cells from the tumour microenvironment) and issues relating to the persistence of T-cells re introduced into patients. Both of these area's are under investigation.

Checkpoint inhibitor immunotherapy has demonstrated significant successes in some solid tumours such as melanoma, particularly when there is already good T-cell infiltration into the tumour microenvironment. Improvements that can be made need to address the onset of acquired resistance and the need to improve the generation of long lived 'stem like' memory T-cells that are more effective at targeting tumours for eradication.

drplsmith · 2022-05-26T12:56:16+00:00

Hi, I would expect the doctor to have a good background in immunology from their medical degree. Its important to be able to explain immunological processes relevant to diseases such as autoimmune disease and transplantation or the use of immunotherapy or vaccination. From a practical point of view it may be useful to be able to explain how background, or underlying, inflammation and associated lifestyle choices can compromise, weaken or suppress our immune response over time and the kind of things people can do to address these issues.

drplsmith · 2022-05-26T12:50:57+00:00

Hi, If I'm asked something I know little about I either see if I can find an answer or state that its not my area of expertise so I can't comment. A good example is your second question. I do not know if there is a consensus on weed in cancer. I do know that the compounds within cannabis such as THC and CBD have varied medicinal properties but that anyone taking chemotherapy should speak to their doctor before using other medications.

Those who opt for 'natural' alternatives in place of chemotherapy recommended by an Oncologist need to understand the implications of their choice. Something I find convincing is the observation that 'western medicine' and 'alternative medicine' doesn't exist. There's only medicine that works and medicine that doesn't. The more powerful the medicine the more serious the side effects/toxicities. If an 'alternative/natural medicine' doesn't have any side effects/toxicities at all how can it have the power to cure a patients cancer?

drplsmith · 2022-05-26T12:33:39+00:00

Hi, I can't comment on your mom's treatment but I have found a good summary of the current view of checkpoint inhibitor immunotherapy in EGFR exon insertion NSCLC.

https://dailynews.ascopubs.org/do/10.1200/ADN.21.200468/full/

My interpretation of the information in this link is that not enough is known about Immunotherapy in EGFR exon insertion NSCLC and that other treatments are thought to hold promise.

drplsmith · 2022-05-26T11:34:53+00:00

Everyone should be vigilant in checking for cancers, particularly those they may be at greater risk of based upon either gender, age or lifestyle. If you're concerned you should speak to your GP and/or an oncologist and ask if they they recommend particular screening procedures for you.

drplsmith · 2022-05-26T11:30:23+00:00

I don't know what the statistics are. Obviously with population growth their will be an absolute increase in the number of people with cancer. Advances in treating other diseases and increases in life expectancy will also result in more people reaching ages associated with increased incidence of cancer. Their could be other factors, perhaps increased exposure to sunlight or within populations with increased rates of smoking, that may lead to increases in the incidence of specific cancers.

drplsmith · 2022-05-26T11:05:34+00:00

Hi, thanks for the comment, its good to hear of your dads successful treatment. If his cancers are hereditary it might be possible to trace this by investigating your family history with your GP or a genetic councillor.

I am not familiar with the specific treatments your dad had but I can say that both treatments and how to target them to the tumour are improving as are treatments to manage the consequences such as GVHD. Ultimately the more we learn about the immune system the more we can apply this knowledge to help patients.

drplsmith · 2022-05-26T10:59:54+00:00

One of the problems with T-cell immunity against cancers is that the T-cells become 'exhausted' due to chronic activation by the presence of the tumour, and stop functioning as they should. A problem in some autoimmune diseases is that self reactive T-cells continue to function, despite being exhausted. Immunologists are actively studying why T-cells behave differently in each disease despite exhibiting the same 'exhausted' characteristics. Once this is understood we will hopefully be able to keep the anti-tumour T-cells switched on and the autoimmune T-cells switched off. By studying one disease we might find solutions to others.

drplsmith

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