INNOVATIONS IN CANCER TREATMENT

Oncology has been expanding at a rapid pace in recent years, to say the least. The latest innovations in cancer treatment transcend new dimensions, previously thought to be restricted to works of science-fiction. From magnetically-guided, cancer-starving bacteria to real-time tumor tracking with nanotechnology, the options on the horizon for those battling malignant diseases are truly becoming sophisticated, pushing the boundaries of cancer research and ever-increasing the promise of a cure at every step.

The progress made in the fields of cancer immunotherapy, precision medicine, personalized onco-treatment strategies and enhanced drug delivery are worthy of special mention. So how close are we to curing cancer? The below review summarizes novel breakthroughs in oncology that may leave you speechless!

New Developments in Cancer Immunotherapy

Cutting-edge advancements in immune modulation are getting closer to finding a permanent solution to combating cancer. Anti-cancer viruses, improved vaccines and genetic immune cell implants are some of the newest cancer treatments that have taken immunotherapy to the next level.

Oncolytic Viruses in Personalized Anti-Tumor Vaccines

Understanding that cancerous cells evade immune responses through unique defense mechanisms has naturally given rise to a call for anti-tumor vaccines. Priming the immune response to the tumor can help the body to destroy it[1].

This is not a new concept. So far, two anticancer vaccines already exist on the market:

• Sipuleucel-T, approved in 2010 for castration-resistant prostate cancer.[2]
• Talimogene laherparepvec, approved in 2015 for unresectable melanomas.[3]

Recent advances in cancer research hold promise for even better vaccines that can target a wide variety of cancer types with a high degree of accuracy[4]. To achieve tumor immunity, scientists have been exploring oncolytic viruses, which are viruses with the potential to demolish tumors. By adding these types of viruses into anticancer vaccines as adjuvants, it is theoretically possible to both destroy a tumor and prime the immune system for a highly effective response against malignant cells.

This concept has already proven successful in preliminary studies and further testing is being conducted clinically in the US and Canada. There are different methods for preparing oncolytic viruses for use in vaccines. The most common one is to insert a tumor-specific antigen into the viral genome, which primes the immune system to the tumor antigen while increasing the chances of destroying the tumor via viral infection. An issue with this method is that the oncolytic virus used is not necessarily going to reach the tumor, infect the tumor cells and promote its destruction. However, it will most certainly prime the immune response to malignant cells.

A revolutionary modification to this approach and potential cancer treatment breakthrough is currently underway to ensure that oncolytic viruses reach their tumor targets. Oncolytic viruses can be prepared with peptides specific to the tumor, which ensures they infect the tumor and not healthy cells. These types of vaccines are less labor-intensive to produce and can be uniquely tailored to each cancer patient, opening a new avenue in personalized cancer treatment.[5] [6]

Further initiatives to improve anti-cancer vaccines are aimed at enhancing synergistic oncotherapies, such as CAR T Cell therapy.[7]

CAR T Cell Therapy

Chimeric Antigen Receptor (CAR) T Cell Therapy is a revolutionary new cancer treatment that improves the patient’s immune response to a specific tumor through enhancing antigen detection.[8] An antigen is a protein that the immune system can register as either self or non-self. Cancer cells typically rely on a number of tactics to ensure the immune system does not register their presence, passing off as a self-tissue. Utilizing the immune system's T cells, CAR T Cell therapy enables the recognition and elimination of tumor cells by overcoming the disguises or defenses of invading antigens.

In the CAR T Cell Therapy process, T lymphocytes (a type of white blood cell) are taken from the blood of the patient for laboratory modification. At the lab, the T cells are genetically altered to produce antigen receptors that can pick up and respond to the antigens produced by the specific type of tumor the patient harbors. Once an antigen is recognized as a threat, antibodies can be produced to neutralize it. This therapy is, therefore, only effective in patients who are able to produce antibodies. Currently, it is only approved for use against various types of lymphoma and/or leukemia, where other treatments have failed to improve outcomes[9].

Tisagenlecleucel (Kymriah), the first approved treatment, has been available since 2017 in Europe and the US. It targets CD19 proteins expressed on the surface of cancer cells in young patients (<25 years old) with B-cell precursor acute lymphoblastic leukemia. It achieved a very impressive remission rate of 83% in clinical trials. Risk of an inflammatory syndrome accompanying the treatment warranted the use of tocilizumab, an anti-arthritic drug that proved to combat this potential side effect within 2 weeks in 69% of the patients. [10]

A handful of treatments have followed suit since, slowly expanding the repertoire of CAR T Cell therapy. The approved CAR T Cell therapies include:

• Axicabtagene ciloleucel (Yescarta), available for several types of relapsed or refractory large B-cell lymphoma[11]. As of 2021, this treatment was also approved for follicular lymphoma after two or more lines of systemic therapy.[12]
• Brexucabtagene autoleucel (Tecartus), treats patients with relapsed/refractory mantle cell lymphoma. Up to 55% of patients experience remission as a result of therapy.[13]
• Lisocabtagene maraleucel (Breyanzi) is another CAR T Cell Therapy for relapsed/refractory large B-cell lymphoma in the event that other systemic treatments didn’t work.[14] 62-65% experienced remission for 6-9 months. Side effects of this treatment appear comparatively worse than others.[15]
• Idecabtagene vicleucel (Abecma) is an approved CAR T Cell Therapy for multiple myeloma (relapsed/refractory) that persists after four or more lines of therapy. Unlike other similar treatments, it causes T cells to target B-Cell maturation antigens.[16] The therapy’s average remission rate is 28%, of which 65% of patients experience remission for up to 12 months.[17]

Unfortunately, these treatments are exceedingly expensive and insurance coverage may only be granted to those who show results after a month of therapy. Other side effects of CAR T Cell therapy can include anemia, severe immune reactions and/or immune suppression, flu-like symptoms, pain, fatigue, secondary malignancies and more.

With the future development of new cancer treatments, CAR T Cell therapies are likely to be available for those with glioblastomas and other complex cancers. Improved tumor infiltration and decreased systemic toxicity are some current aims of researchers attempting to improve this therapy.[18]

Innovations in Tumor Targeting Precision

Cancer is renowned for being difficult to treat. One of the main problems is drug delivery to the site of the tumor, which is not always optimal. Strategies are currently being developed in order to improve treatment precision and tumor tissue specificity.

Guided Gold Nanoparticles

Among the latest advances in cancer treatment, Gold nanoparticles have been gaining a lot of traction in recent cancer studies. They have multiple synergistic properties that could serve to destroy tumors or promote drug delivery into them. Gold is magnetic and nanoparticles of it can be directly drawn towards tumors using magnetism. Once there, they can obliterate the tumor when infrared is applied to heat them up. This also implies that patients with gold particles may enhance the destruction of their tumors when exposed to sunlight or other light sources containing infrared.

Nano gold particles have proven to be highly compatible with already existing drugs, able to chemically bind to them with ease. Combinations are being explored in the context of creating very potent anti-cancer solutions. [19]

Over and above gold’s unique tumor-reducing properties, it may also be used as a way to keep track of tumors in the body. Gold can be seen on x-rays and is compatible with many other compounds which can be used to bind the gold to the tumor. Alternatively, gold in drug preparations can show if the drug has reached the tumor on an x-ray.

The safety and efficacy of gold nanoparticles is still being evaluated. Preliminary evidence suggests that excessive nanogold particles may be toxic to connective tissues in the body.[20]

Magnetic Bacteria

In a similar fashion to gold, there are some strains of bacteria that are highly magnetic and that also may be able to take out tumor cells. These bacteria appear to store iron in larger quantities, conferring their magnetic responsiveness and may be able to starve some tumors of this prime nutrient[21]. Preliminary experiments have proven successful in using magnetism to guide such bacteria in biological systems[22].

The bacteria may also be able to act as carriers of anti-tumor substances or nanoparticles that can enhance this strategy. Combining this with a therapy that enhances immune recognition of the tumor may be a winning treatment option in the years ahead.

In spite of the promise this holds, much more work needs to be done in order to verify how such bacteria might interact with our biology.

New Anti-Cancer Drugs and Drug Enhancements

While many drugs are continually being tested for their potential in demolishing malignancies, only a few actually make it to the shelves. Of those that have, their efficacy has been questioned due to poor drug delivery to the site of the tumor. These drugs are constantly being re-tested with modifications to enhance their anti-cancer actions.

Novel developments in this field have also given rise to far better medications, improving the prognosis for many patients.

Sotorasib: the First-Ever KRAS Inhibitor

Also known as Lumakras or AMG 510, this drug was shown to inhibit a mutant KRAS protein that seems common to several advanced cancers. KRAS genes that produce this protein are involved in regulating normal cell growth. Mutations in the gene cause the protein to become a fixed signal for perpetual growth and induce cancer formation. In spite of being one of the first discovered tumor-forming mechanisms, the KRAS protein has proven one of the most difficult to target, being regarded by experts as “undruggable”.[23] [24]

Almost 40 years later, the first-ever KRAS inhibitor is now available on the market. The drug is FDA approved for non-squamous non-small cell lung cancer[25] for which it proved most effective against[26] and may be promising for treating a variety of other tumor types. Since not all tumors possess this mutation, lab work confirmation of the KRAS mutation is necessary before the drug can be prescribed.

Recently Approved Anti-Cancer Drugs

As of 2021, a few new anti-cancer drugs have been approved for use[27]:

• Relugolix (Orgovyx) treats advanced, castration-resistant prostate cancer by suppressing the release of pituitary hormones.
• Tepotinib Hydrochloride (Tepmetko) may help those with metastatic non-small cell lung cancer who have a specific MET gene mutation. The drug inhibits this gene, slowing cancerous growth in this case[28].
• Umbralisib (Ukoniq) inhibits PI3K delta (phosphoinositide 3 kinase delta) and CK1 (casein kinase 1); approved for treating relapsed/refractory marginal zone lymphoma after anti-CD20 treatment or follicular lymphoma after three lines of systemic therapy.[29]

Nano Drug Delivery Enhancement of Pre-Approved Cancer Drugs and Treatments

Many pre-existing cancer drugs that have already shown efficacy against specific tumor and cancer types have been modified with nano-particles for enhanced delivery to the target tissue site. The new renditions of these formulations could prove more potent and precise, as nanoparticles are readily absorbed by cells with minimal difficulty. More than 100 drugs have been modified in this fashion and are currently undergoing clinical trials. [30]

The nanoparticle infusions are typically specific to the cancer the drug is aimed at treating, with various nano proteins such as albumin, lipids, mineral and carbon particles being employed to enhance drug delivery[31]. Synthetic hormone analogues are also being investigated to enhance delivery, including somatostatin for colorectal cancers.

Nanoparticles and devices[32] are also being studied for their potential as unique bio-tracking devices that are able to give a more precise indication of tumor status. This might be achieved through small-scale electronics (i.e. SMART nanotechnology), fluorescent nanoparticles or through simplistic tests (urine/ blood tests) that can read implanted nanoparticles as markers of disease progression. Some of these may be able to enhance surgical removal of tumors too.

Newly Discovered Anti-Cancer Effects of Common Painkillers

It seems like some common over-the-counter painkillers might offer a surprising degree of protection against cancer in high risk people with lynch syndrome (a type of hereditary benign colorectal cancer) and the elderly. Both the NSAIDs, aspirin and naproxen were shown to decrease the risk of contracting colorectal cancer in regular users of these drugs. Aspirin use for 5 years before age 70 has been shown to lower the risk of colorectal cancer in elderly patients by up to 20%[33].

The anti-inflammatory nature of these drugs appeared to confer some degree of protection, while naproxen additionally promotes the recruitment of immune cells to the colon. This lowers the chance of malignancies escaping immune vigilance.

Naproxen has also proven to confer a much higher degree of protection against cancer than aspirin, which would need to be used in much larger quantities and on a long-term basis to achieve similar anti-inflammatory results. Scientists are investigating the potential of naproxen as an anti-cancer vaccine adjuvant.[34]

Innovations in Personal Medicine for Cancer Patients

New treatments for cancer have certainly progressed by leaps and bounds in the last couple of years, especially with respect to bettering patient outcomes. While treatment options are still largely restricted for many types of cancer, it is becoming widely acknowledged that cancer is a complex disease with each case demanding a unique treatment solution.

Tailored Treatment Promotes Life Extension

The newest cancer treatment advances involving personalized medicine and care have been becoming more refined, which has subsequently proven to extend the lifespan and prognosis of cancer patients. More physicians are starting to catch on to a personalized approach, taking multiple more aspects of the patient’s health into consideration than was previously thought relevant to treatment. When factors such as genetics, immune function, hormones, other disease states, nutrition and tumor-specific markers of the patient are used to build a more accurate picture, better treatments are selected that are less prone to producing adverse effects. This alone is enough to enhance the quality of life for the patient and has additionally been shown to improve disease prognosis.

Immunotherapies are of particular importance among new treatments in cancer care. Targeted combinations of immune-enhancing drugs that have been chosen based on the immune profile of the patient are better tolerated and yield a larger degree of success. Such combination immunotherapies are showing promise in treating various types of cancer and have been a focal point of many studies. For instance, a study by oncologists in Spain utilizing combination immunotherapy showed improvements in quality of life and associated symptoms among patients with relapsed or refractory multiple myeloma. [35]

Better Genetic Markers for Oncogenic Drivers

It has become increasingly clearer that an over-arching view of oncogenic drivers is required for effective cancer treatment to take place. Oncogenic drivers are genetic factors that contribute to tumor formation and that also give information about tumor defense mechanisms. There are hundreds of failed clinical trials with regard to cancer therapies that target single mechanisms only to give rise to new cancerous mutations, higher resistance and sometimes even metastasis.[36]

For some cancer types, more oncogenic drivers have been identified that have improved the accuracy and efficacy of treatments. This field of research highlights that targeting multiple pathways is likely to be more effective than targeting a single pathway. Thanks to new cancer research and developments, many combination therapies specific to the patient are now being used to improve prognosis in cancer patients.

Patient-Generated Health Data and Integration

In the past, a patient would have needed to get an appointment and sometimes opt for lab tests to decipher what is truly going on in their bodies. This process is slow, tedious and prone to inaccuracy, often requiring multiple trips, tests and expenses. Devices have begun to emerge that can take blood pressure, heart rate, skin conductance and more. The readings taken by these devices can be monitored real-time and present a more accurate picture of the patient in a number of settings.

While these technologies are being used with great success in treating a few other health conditions, such as epilepsy, stroke, heart disease and diabetes, developments for cancer patients are still underway. Nevertheless, many cancer patients present with one or more comorbidities, in which these devices can prove useful for enhancing oncotherapy.

Apps and further technology have been developed and are being refined to enhance the seamless integration of health data into the patient’s file. This includes the integration of real-time patient-reported outcomes in which the patient constantly provides feedback pertaining to symptoms. Meta-analysis reveals that often, patient reports can predict whether a tumor treatment is working or not for the patient. Instant patient feedback has been used to tailor treatment plans at precise intervals, which has improved patient outcomes and increased the survivability of such patients. Furthermore, this data can be used to improve the prediction of prognosis and mortality for several types of cancer, including multiple myeloma, castration-resistant prostate cancer, early stage colorectal cancer and advanced cancers in general. [37]

Artificial intelligence is also being explored[38] in order to structure all this information in a way that helps the practitioner to quickly analyze the data and make better treatment plans for the patient. Algorithms already exist that can help to identify and prevent potential states of disease before they arise based on patient feedback and self-presentation of symptoms. Incorporating AI can be a cancer breakthrough with potentially significant implications, offering new avenues for personalized therapies.

The Impact of COVID-19 on Cancer Therapy

The COVID-19 pandemic has brought to light a need to reassess oncotherapy options in some cancer patients who are likely at a higher risk.

In a study assessing nearly 5000 patients, many cancer-related markers proved to increase the risk of contracting severe COVID-19 with SARS-COV-2 infection. Of these, the elderly, those with hormonal cancers and malignancies of the blood, as well as those who are opting for chemotherapy appear to be in the worst risk category. Several other studies have investigated the impact of COVID-19 on people with specific types of cancer, such as this study involving patients with hematologic malignancies undergoing cancer treatment in Spain.[39]

Specific chemotherapy treatments associated with worse severity include R-CHOP, platinum-etoposide chemotherapy and DNA methyltransferase inhibitors. These treatments are linked to a significant risk of 30 day all-cause mortality as a result of COVID-19.[40]

In the Pipelines

New lines of research have opened up previously unfathomed treatment avenues for those with advanced cancers. A sneak peek at the possible options the future may hold for these patients include:

Targeting the Circadian Clock of Tumors

Just like all ordinary cells in the body, tumors appear to have their own biological clock that responds to circadian cues. Unlike healthy cells however, tumors have a slightly warped circadian rhythm and seem to respond better to unbalanced hormonal signals that arise from an out-of-sync bio clock. This is highlighted in studies revealing that animals and humans with optimal circadian rhythms tend to survive for longer, having a better cancer prognosis.[41]

Recent advances in this field have discovered several circadian signaling compounds that have anti-tumor actions, capable of promoting their destruction and clearance[42]. These cell signals are also able to promote the removal of aged cells that, while non-cancerous, are able to secrete factors into the tumor microenvironment that enhance cancerous growth. Scientists speculate that circadian biology, decreased cell turnover and faulty cell accumulation may be major factors involved in the increased risk of cancer in the elderly population.

Furthermore, circadian factors are very important in regulating the function of the immune system, including its ability to target cancerous cells. Disruption in the circadian cycle alone can predispose one to develop cancer and other chronic illnesses due to the negative impact on the immune system. Currently explored drugs that improve circadian signaling are showing promising results in preliminary studies, with the potential to enhance immune function and reduce the adverse side effects associated with cancer therapies.[43]

In the next few years, it is anticipated that circadian hormone modulators will become both an attractive anti-cancer strategy and complementary treatment, particularly in the elderly and those who struggle to maintain a healthy bio clock.[44]

Other Developments

The biggest developments currently underway are all focusing on the elusive nature of complex solid tumors in the advanced stages of malignant diseases.

• Precision Diagnostics for Complex Tumor Types to Improve Disease Prognosis and Treatment

Some tumors, such as glioblastomas, consist of multiple tumor types that grow together. Profiling of such tumors has revealed that each tumor may constitute unique genetic markers and may have to be targeted in different manners for optimal success. In time, a complete understanding will be rendered that will likely improve the prognosis of these otherwise deadly complexes.

Experts are particularly keen to get markers for the microenvironment of tumor collectives so that precise action can be taken to improve immune recognition and destruction of them.[45]

• Liquid Biopsies for Advanced Cancer

Currently available blood tests (also called liquid biopsies) can pick up some preliminary markers at the early stages of cancer[46]. While these have proven successful in early detection, biopsies are currently the golden standard for tracking the progression of advanced tumors.

Biopsies substantially increase the risk of metastasis, where the cancer spreads to other body sites and multiple more tumors begin to grow. Better liquid biopsies are being developed that make use of a highly sophisticated consortium of markers to track the progress of advanced cancers in a non-invasive manner that does not risk metastasis. Not only is this a much safer approach, but it will eventually become a cheaper alternative to conventional biopsy that can be performed as often as required.

• synNotch-CAR T Cell Therapy

Scientists are developing forms of CAR T Cell Therapy for solid tumors that are complex, such as glioblastomas, ovarian tumors and mesotheliomas. These tumors tend to be better at confusing immune cells and don’t have a single identifiable antigen that can be targeted in order to nuke all the cancer cells in one shot.

In order to work around this, T-cells were modified to allow them to respond to a main “priming” tumor-specific antigen, as well as one or two other antigens that are secondary. These secondary antigens may be found in normal cells, but the priming antigen makes sure that the immune cell only targets them when found in cancerous cells subsequent to the priming antigen.

Mice studies showed a longer lasting remission in response to this therapy compared to others of its kind. Further antigen combinations are being explored for improved efficacy.[47]

Conclusion

The above advances in oncology highlight the importance of personalized medicine in the context of treating all types of cancer. Better biomarkers, real-time data collection and greatly improved AI integration are all changing the face of personalized medicine, particularly with regard to cancer treatment and prevention.

Latest cancer treatments incorporating combination targets and therapies are replacing most treatment options at a furious pace, with a higher degree of accuracy tailored to the patient in question. Nanoparticles are becoming a standard part of oncotherapy through improving anti-cancer drug delivery and efficacy; with room for use in tracking disease progression. Vaccines in combination with genetic enhancement of the immune system (CAR T Cell Therapy) may serve to provide long-lasting immunity against cancer in time, greatly enhancing prevention. Moreover, infections with anti-cancer viruses and/or bacteria may be a winning solution that can be used in combination with current immunotherapies.

Lastly, the discovery of protective benefits pertaining to everyday anti-inflammatory drugs inspires the hope that prevention might be more accessible than previously thought!

 

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